Italy in late April and early May

FLIGHTS: First of all I always recommend the reverse itinerary, that is fly into Venice VCE and return home from Rome FCO. The reason is the distance of those airports from their respective city centers. VCE is far in the mainland while the historical center is in the middle of the water. Since flights to North America depart in the morning, departing from VCE means having to catch a boat before 4am. FCO, on the other hand, is only 30-35 min from the city center of Rome by taxi or train.

WEATHER: generally nice and mild but rain very possible too. Hard to predict this far in advance. Check weather websites just before departure.

CROWDS: April 25 is a national holiday (25 Apr 1945: Liberation day, end of WW2 and nazi occupation in Italy). May 1 is a national holiday in Italy and throughout Europe (Labor Day). That period and the weekends around those holidays is the busiest tourist time of the year. Make sure you book accommodations timely especially in Rome, Florence, and Venice. Outside of that period, you should have no problem finding vacancies, but there will be lots of tourists regardless.

I've been to Italy three times, all in late April. Weather has always been perfect - maybe had one day where it rained for an hour. Otherwise sunny, warm, but not too hot. You'll have some crowds at the big sites, especially in Venice, but I don't think it was ever horrendous. Especially if you take advantage of the tips in Rick's book to beat crowds, you'll be fine.

As always, Roberto's right on the money.
When flying out of FCO, be sure NOT to get one of those famous 6:00 a.m. flights. They all fly to another European Gateway airport where you'll sit around until mid-day before taking another flight to North America. It's bad enough flying so long, but it's even worse when you have to get up 6 hours too early to make a flight on time. Try to find a flight directly to North America late a.m.
We would never go to Italy in the Summer--preferring to go in April-May or Sept.-Oct.

I understand the logic of Rome being easier to get to early in the morning but would question whether you save any time.
In my experience flying out of both, Rome's airport is so much larger that you need to arrive much sooner before your flight than Venice.
Venice especially early is very slow and from what I heard many times from others never has a long line early in the morning.
It does cost more but if you take a private water taxi from the center in Venice the ride if you are tired in the early morning is far enjoyable than a taxi to Rome's airport from the center.
So for the same time flight I likely could sleep later in Venice and have a more pleasant morning.

Not really trying to debate the point, just stating that I am not sure it makes that big of a difference.
Rome offers more flight choices to most destinations especially to/from the US but either one is unlikely to be direct for most US tourists.

We are going April 26-May 10 out of SFO. Second trip. Our (UA)flight home is late morning Rome FCO going direct to east coast city. There were other flights at that time direct to other east coast cities from FCO with same carrier. If you fly to the US mainland from FCO they have you go to terminal 5, and as I understood, the security run through is a bit more time consuming or for some reason more time is needed before boarding.
Starting out, I think if we had chosen to fly into Milan we might have had a solid chance of a direct flight from an east coast city, if not from SFO. But we chose Verona to start, so we are going through Frankfurt to Verona and now have to catch the train to Venice that day. My fault for changing my mind on Verona as a base after we bought tickets. On our first trip we had fewer stops but still went through Heathrow to Rome and back same route. We found we like to use Rome as the last day or two of the trip, its not our favorite place, but do like Trastevere a lot The hotel was great about calling a cab for us and our cab driver gave us an enjoyable ride to FCO, about 35-40 minutes from Piazza Navona area. We were able to catch a bite to eat and coffee, hotel started serving at 7 am, head to FCO at 7:30, flight was at about 11 to Heathrow.

Weatherwise will be more iffy. Two years agowe were outside of Florence for a week. It rain lightly every day. The morning were very cool and damp, sometimes rain and then the rest of the day was fine. Others were reversed with afternoon showers. Never heavy, just a light, gentle spring rain. Not a problem other than being sure to have a rain jacket and umbrella every day. We prefer the Sep/Oct period because it is dryer and warmer.

I would do Venice first because you can get direct flights to the US from Rome starting late morning. Flight options out of Rome are better. Venice almost always requires a very early morning flight to a connecting city somewhere in Europe.

Venice is a better place to start for other reasons too. Venice is low key and (please don't take offense, anyone) without major (aka intensive) sights. You can wander the back canals, ride the vaporetto, sit at a cafe, and soak up the atmosphere while getting over jetlag. Rome is a big noisy, bustling city and it's harder to enjoy the Vatican or the Colosseum when you're wiped out from that long-haul flight.

I think your dates are an excellent choice, weather-wise.

Thanks everyone for your replies. The flights I've been looking at out of Venice are at 12:00 and 1:00, with a layover in Rome or Paris, so I'm less worried about that. Though flipping to order of the trip is interesting. As for Labor Day, is it worth moving when we go to avoid it? We don't mind crowds and if there are any labor day events that could be interesting. But we do have a lot of flexibility as to when we go. Based on a very loose itinerary we would likely be at an agriturismo in Tuscany, around Siena. Planning to visit wineries, Sienna, San Gimignano, Volterra and the country side. I figure being out of the the bigger cities will help with the crowds. Since Labor day is on a Tuesday next year, will it be celebrated on Monday (ie will things be closed on Monday or Tuesday)?

ttmom12 - What was the name of the hotel you stayed at in Trastevere. I was thinking that area would be a good place for us to stay.

Agree you should start in Venice for the reasons Chani mentioned. Venice is a much better and easier local in which to acclimate. Very laid back and slow paced as opposed to the hustle and bustle of Rome.

May 1st (Labor day) falls on a Monday in 2017.
April 25th (Liberation day) falls on the previous Tuesday.
There will be marches and public gatherings organized by workers' unions on May 1st and various WW2 commemorations on Apr 25.

It's not a matter of crowds in the streets, as crowds of tourists will be present throughout the Spring and Summer months in the big 3 city destinations of Italy (Rome, Florence, Venice), no way to get around that. However finding accommodations during the period from Friday April 21 through Monday May 1 will be more challenging in those cities, therefore I only recommend that you don't wait till the last minute to book hotels, because you may be left with less desirable choices.

As to the flights out of VCE, yes there are a couple of flights directly to the US which depart a bit later in the morning or after noon (AA to PHL, UA to EWR, Delta to JFK or ATL), although not sure if they operate in April, since they are seasonal (with the exception of the Delta to JFK, which operates thorughout the year). However I doubt there are flights as late as you say that can get you to the US on the same day via CDG or FCO. I'm not aware of flights to the US from either FCO or CDG departing after 2pm. Therefore if you depart from VCE at Noon, you won't make any of those flights and you will likely need to spend the night either in Rome or Paris. I recommend you check your flight options again.

Be aware that Apr 25th is also the Feast of St Mark, patron saint of Venice. Rick's book mentions a tradition of men giving their women a rose to commemorate the day. I'm guessing St Mark's might be a little busier than usual, but I don't know of any specific events going on. We arrive in Venice on the 23rd, so we'll be there for any festivities.

tDurkee re hotel in Trastevere:

We stayed very close to Piazza Navona at a small boutique hotel called Palazzo Navona Hotel. Its one street over from Piazza Navona, so its easy walk to Trastevere. Its also a very quick walk to the Pantheon, passing by a great coffee shop on the way. It has a nice roof top bar with great views. One thing we did not like was being given a room next to the stairs and lift, the floors are stone without carpet. Foot steps permeated the wall into room. Good place if looking for better than average place to sleep with a great location between Pantheon and Piazza Navona. Nice contemporary place. However Trastevere would be an excellent place to stay, lovely area with more relaxed pace and very good restaurant options. Despite all that, this trip I opted to stay right in front of the Pantheon. (A wonderful cellist played incredibly beautiful music there one evening of our last visit, he was just amazing. Hoping he comes back while we are there as I will be hoping to listen again)