Milan

I really cannot help on the Milan aspects.

The 2 side trips you mentioned I can comment on:
Venice: a place I loved in the early morning hours from before sunrise to about 10 AM and then liked a good deal after dark ; also a place where although it was cool to see I disliked it during the midday in Sept. More crowded than anywhere else I have been in Italy and made it tough to walk let alone enjoy much of anything. Tour groups were the worse offenders. Sure you can get to a back street/canal which is free from the mass tour groups and have some peace but if your only time there is a midday 5-6 hour window then you need that time to see the crowded sites.
My point being if you want to see it you should do an overnight so you see it in it's best hours rather than as a daytrip from Milan where the time you will be there will be the most crowded.

Cinque Terre:
It is a bit of a hassle to get to, lovely in Sept and definitely recommend going but staying 1 night would not be enough time for me. Although the trains are fairly frequent the timing hopping from town to town if you want to see many of them just eats up too much time in the day.

There really are no hotels in 4 of the 5 towns, only Monterosso (for many their favorite town, for me my least favorite town of the 5). The places to stay are more B&B or more accurately for most Bed without Breakfast. We stayed at a B&B (no breakfast) in Manarola with amazing ocean views, it was lovely and loved the beauty of the Cinque Terre. Our place though like many was a good hike from the train or car park areas (not so far distance but all uphill with steps as well). Point is I wouldn't want to deal with the hassle that was check-in/checkout here for only 1 night. 2 or more nights would be different and give you enough time to see the different towns. Just my opinion if you are traveling light from Milan an overnight here maybe can be fine and better than a few hour only day trip.

We did do a day trip to Verona and I thought that was the perfect day trip place. The center part of town is small, lively and multiple sites/things to do in close proximity so really a perfect day trip destination. The Juliet balcony gets crowded like Venice but that is only a small site and the rest of the city center has ample room for crowds. My wife felt the shopping in Verona was as good or better in all of Italy (we didn't go to Milan).

Lucca and Pisa would make a good day trip I think.

If interested in tours or a driver to visit other areas, I can recommend:
Elisabetta at Professional Tour Tuscany
professionaltourtuscany@gmail.com

We are planning on booking our Last Supper tickets early. Should we go on our own or with a tour?
If reservations are difficult to get on those dates, a tour is the way to go.

Is it too much to do one the first day we arrive? Flying JFK to Milan direct.
No, if you have the tour/reservations booked already.

Also best way to get to Milan from airport? Pre Book?
No. Since you arrive to MXP, which is far from the city, the fastest and cheapest way is the Malpensa Express to Milano Cadorna station, which is closer to the center (and also faster trains) compared to the Milano Central station.
Timetable below. Don't book anything since you don't know if the plane will be delayed. Just buy tickets at the airport station on arrival:
http://www.malpensaexpress.it/en/

We are also planning on a day trip to Venice and an overnight, 2 days in Cinque Terre.
Can you spare a couple of nights in Venice? It's worth it. Do you need to be in Milan for the whole 2 weeks? Are you there on business? All there is to see in Milan can be seen in a couple of days. I don't see a reason to spend 2 weeks in Milan unless you are going there for work/conferences etc.

Any suggestions for hotels in Cinque Terre. We plan on taking the train, touring and stopping overnight, touring the next day and returning to Milan. Where is a good stopping place?
Not sure what you mean. Stopping where? between Milan and CT?

Should we do a combination of tours and exploring on our own?
On your own would work.

Suggestions for tours and tour companies?
No suggestions. Maybe others can help.

Thanks for the quick responses.
If I recall correctly the train stations in Milan have a lot of steps and some of my group cannot carry luggage and others are taking too much luggage!!

We booked an apartment via air bnb as a home place.
Any thoughts about going to Ravenna?
Thanks

If you follow my advice to take the Malpensa Express to Cadorna, there will be no stairs there.

For your day trips you will need to go to Milano Centrale, which has stairs but also escalators.

Ravenna is 2h45min from Milan by train (change in Bologna)

The comprehensive array of escalators at Milano Centrale is probably new since the last time that you visited. The main places that your over-packers will have trouble will be in the Cinque Terre (most stations have stairs as well as some accommodations) and Venice (where many bridges and hotels have stairs).

Ravenna is fabulous. A bit off the beaten path so not overwhelmed by tourists. You can visit Ravenna on a day-trip, but do try to get an early start since it's a bit of slog from Milan (you change to a regional train in Bologna for the last little bit). There are 6 or 7 mosaic sites. You don't have to see them all, but they are all worth seeing. One is a little way outside of town, easily accessible by bus but possibly affordable via taxi for your group. In addition, the town itself has a beautiful historic district of fair size where you could wander for at least a few hours, just enjoying the beauty. Highly, highly recommended.

Other very nice cities you might research to see whether they sound appealing to your group:

• Bergamo, a historic hill town (take the funicular up) that's only about an hour from Milan via relatively inexpensive regional trains running roughly twice per hour. An easy side-trip. It would be a shame to miss it.

• Lake Como. The favorite Lake Como town seems to be Varenna, which is about an hour from Milan via inexpensive regional trains running every hour or two. From Varenna you can get a boat (or a bus) to visit other towns along the lake. Barring dreadful weather, I'd consider this a must. Lake towns just feel different from other places.

• Bologna, a big city (major rail junction) with a large and attractive historic district. Known for fabulous food. It's fun to wander the streets in the bustling old town, which are mostly arcaded, so this is a great destination if you hit a rainy patch. The core of the historic district is about a 20-minute walk from the train station, so research buses ahead of time or plan to grab a cab.

• Vicenza, which has a smallish and very walkable Palladian historic district. Between Verona and Venice and just under 2 hours from Milan by train. Attractive and architecturally rather different from my other suggestions. The walk from the train station to the historic area isn't bad at all.

• Padova, home of the Scrovegni Chapel (timed ticket required, safest to order a bit in advance) and an interesting historic district. A bit over 2 hours from Milan, just beyond Vicenza on the rail line to Venice.

• Stresa on Lake Maggiore, the starting point for boat trips to the Borromean Isles. An hour to 90 minutes from Milan by mostly regional trains--reasonably frequent but not quite hourly. Stresa's an old-line lake resort, attractive enough but to me not ultra-compelling. I wouldn't go without confirming the running times of the boats to the Isles, which are quite interesting.

• Ferrara. Everyone here who has seen it (I haven't) seems to really like it. 2:15 to 3:30 from Milan, changing in Bologna.

• Modena. Also recommended by others here. 1:40 to 2:45 from Milan, with at least 3 trains per hour.

Just looking at a map I see a number of other cities I've read about but haven't visited. What I'd do is pick up a guidebook that covers northern Italy rather comprehensively, put together a list of possibilities, then stop in at the Milan tourist office early on. Ask about special events and places within an hour or so (since so many of my suggestions will take twice that long or more).

Trips involving Freccia trains (not Varenna, Bergamo or Stresa) could be quite expensive if you buy the tickets at the last minute. You can save a lot of money--at least half the regular ticket price--if you are willing to commit to a particular Freccia or other fast train on a specific day and buy the tickets when they go on sale (probably 120 days ahead).

You do not need a tour for any of these destinations. A tour could be helpful for rural destinations (wineries, etc.) or to visit multiple small towns in one day. I believe each of the above destinations is worth a day by itself. I know the Bologna tourist office does walking tours, and I think Vicenza does also.

If you decide to do a tour to get Last Supper tickets, Walks of Italy has a great one called Best of Milan. It's a 4 hour walking excursion though the center and includes not to miss sites including da Vinci and the spectacular Duomo. Agree with others: not sure why anyone would stay so long in Milan, and for Cinque Terre you need at least 2 nights to see much of anything, even if you're not hiking the trails. Monterosso is a really nice place to stay and La Spiaggia is an excellent small hotel. In Monterosso you will see lots of people, but it's more spread out because of the wide beach and you won't feel like you're suffocated by mobs of tourists packed cheek by jowl like in Vernazza. It's terrible there now, IMO.

I often stay a day or two in Milan during each trip to explore new areas and re-visit old favorites. In addition to the obvious Duomo and Last Supper, spend time at the Brera and Ambrosiana art galleries. The Poldi Pezzoli and Bagatti Valsecchi are both interesting and remind me a bit of the Frick in NYC. Sforza Castle and the flea market at Navagli are also worth visiting as is a tour of La Scala. By suburban train you can get to Pavia - the Certosa is spectacular. Tour is in Italian, but still worth doing even without language facility.

To the list of already suggested day trips I would second Bergamo and add both Mantua and Parma. Mantua has two exceptional sites: Palazzo Te and the Ducale Palace. Parma has a beautiful cathedral and Baptistry, art museums, and some of the best food in Italy.

As for tours, check with tourist information offices in your destination cities. Often they have English speaking tours on specific days.

Milano is in Lombardia, not sure a tour guide from Tuscany will accommodate you for day trips.

Ferrara and Ravenna, by all means, if you can stay in Bologna for a few nights.

If you buy train tickets early, up to 120 days in advance, you can get a Milano Centrale-Venezia Santa Lucia ticket for €7 (unless prices change).

I would spend at least a night in Venezia, preferably more.

Best way from the airport might be the Malpensa Express, which goes to either Cadorna or Centrale stations, make sure you are at the right track. For four of you, a taxi (from the official rank) might be worth the cost, the ride is about an hour.

Milano Centrale has elevators as well as moving ramps. No stairs necessary inside the terminal. There may be a short flight at the entrance, but there are several exits/entrances at the front of the station and I think stairs can be avoided completely.

I must say I am very appreciative of all the responses.
Keep them coming!!
Grazie molto!!!

Joyce,
We were in Ravenna in February. This is worth the time on a train from Milan and then some. I found it hard to leave but an experience I still regard as the best experience of our time in Italy. San Vitale is beyond incredible. I missed the Basiilica just a cab ride outside of town, so hope you don't miss it. The town is easy to navigate on foot, the flat bread and fig sauce at the café on the piazza wonderful. Enough people spoke English, they treated us so kindly. Just remember to validate your ticket before boarding the train and keep your passport with you. We were asked for ours on the return. The yellow opera house is beautiful. A mom picking up her kids at an elementary school stopped to help us with our map, just offered to help. So my vote is two thumbs up for Ravenna.

You can also get to Sant'Apollinare in Classe by bus, I think it's the #4, but check on that.