Traveling to Florence, fly into Florence or Rome (or Milan)?

If you can make the timing work, there are two direct trains a day from Fiumicino airport to S.M. Novella (Florence's main train station). They depart at 11:08 and 15:08, and take 2 hours, 14 minutes from point to point.

Other trains to S.M Novella involve just a single change in central Rome (Termini or Tiburtina) and can take as little as 2 hours, 24 minutes or so, including the train change. Fastest trains from Malpensa will involve at least 1 change and take abt. 20-25 minutes longer.

if you don't plan to visit Rome or Milan at all, and Tuscany is your only destination, then flying to FLR will nearly always be cheaper. I say this from personal experience since I go to Florence every year. Unless I need to go to Northern Italy or Rome for other reasons, flying to Rome or Milan makes sense only if flying to those cities is at least $300 cheaper than flying to FLR. That nearly never happens. Flying to Rome or Milan is rarely more than $50-$100 cheaper than flying to FLR.
If I don't need to go to Rome, that saving is not worthwhile for me. That is because flying to Rome will entail having to take the train back and forth (over $100) and also spend my last night in Rome to catch the morning flight out. That is at least $150 for the hotel in the ugly Termini area plus $60 for the taxi.
If Rome is part of my itinerary (I have relatives in Rome I occasionally visit) then flying to Rome may still make sense. But otherwise I fly to Rome only if I'm flying with a mileage award (i.e. for free) and it's hard to use mileage to FLR since those mileage award seats are limited.
In your case however, there is an additional factor to take into consideration. That is the convenience of a direct flight. From JFK you can fly non stop to Rome or Milan with no layovers. That is a convenience that you won't have if you fly to FLR which requires a layover in Europe. In my case that is not a factor, since there are no direct flights from SFO to Italy and therefore I must have at least one layover regardless.

Assuming Tuscany is your only destination, and you don't care to go to Rome or Milan, consider flying to Rome or Milan only if you are considering a non stop flight. If you are looking at a flight that gets you to Rome or Milan after a layover somewhere else in Europe, then it makes more sense to fly to FLR, even if marginally more expensive.

Between Rome FCO and Milan MXP, Rome FCO is easier and faster to reach from Florence.

No matter where you fly to, you will need to spend the last night at a hotel in the city you depart from because flights to North America depart in the mornings.

If you depart from FLR, it is therefore better that you leave your Florence visit (your 4 days) for last, and you go to your Tuscan hill town first when you arrive.

As always, Roberto's advice is logical and noteworthy. But I'm still going to give my 2 cents worth.

Any way you look at it, getting to Florence will require a connection somewhere. Arriving in either Milan or Rome (and I agree Rome makes more sense) means wrangling your luggage onto a train (possibly 2).

I fully admit to preferring the easiest way possible. I'm always affected by jet lag on arrival day, and am definitely not mentally sharp. If I can avoid the hassle of train travel right after arrival, I will. I'd much rather connect to a flight to Florence at one of the European hubs. ( with the connecting flight on the same ticket, of course). Then just hop in a taxi to your hotel.

I'd still spend your arrival day in Florence. Use that day to start getting over your jet lag. Take Rick's recommended walks. Head up to San Miniato or Piazzale Michaelangelo. Lots of fresh air. No museums. Then head out to your Tuscan town the next day. Return to Florence for your last 3 nights, get the Firenze Pass if you want it, and go nuts with all the Museums and churches.

Thank you for all the helpful replies, they have given me a better feeling for the proximity of the cities and the total travel times. I was considering flights to Rome or Milan only because they were nonstop, I wasn't planning on visiting either city on this trip (I have been to Rome before). I was figuring that the trains could be a good option but since the trains would be well over 2 hours, not including possible wait times, I think it would be far less stressful to arrive in Florence by plane. I would plan on being in Florence the last night as well, as far as the rest of the trip I will be flexible depending on hotel availability, I would like to use Sienna as a base for exploring the hill towns, I am assuming it would be better to avoid weekend nights?

Weekdays or weekends make little difference. If you plan to visit smaller towns by bus, then it matters, because extra-urban bus service is limited on Saturday and nearly non existent on Sunday, so stay put in town on Sunday if you don't rent a car. But if you rent a car, for those trips, then it doesn't matter. October is not the busiest time of the year, although if the weather is nice, Italians like to take their families out of town on Sunday, therefore you might get into some traffic on Sunday evening, if you drive. City buses and intercity trains operate everyday. City buses are slightly less frequent on Sundays, but not by much. Besides you don't really need buses in Florence. The historical center is about 2 square miles, if that, so you can walk everywhere. Siena is even significantly smaller.

From downtown Florence to the FLR airport, it is a very short distance (about 3.5-4 miles), so the taxi ride is only 15-20 minutes. The taxi fare is 23 euro, plus night surcharge is before 7am, and 1 euro per bag. 30 euro is the most you can possibly spend. Florence airport is small and flights are very few (mainly to the major European hubs) and aboard regional jets like the 100 seater A318, Embraer 190 or Bombardier C100. Check in never takes more than 5 minutes, and walking from the check in area to the boarding gate is shorter than from my house door to my mail box outside. So feel free to get to the airport just one hour before departure, and you still have time for breakfast.

Be aware that due to the extremely short runway flights are often canceled when there are high winds. That doesn't happen every day, but with nasty weather it does. When it does, they might take you with a bus to Bologna, where you will depart the next day after a night spend at the Sheraton Hotel at the Bologna airport (everything is paid by the airline). If it happens when you arrive, you'll simply land in Bologna (or Pisa) where a bus will get you and take you to Florence. Hopefully it won't happen to you, but occasionally it happens (to me twice in about 30+ trips to FLR), but just wanted to mention it as a possibility, in case you need to make it back to work the next day after you return (so get an extra day off just in case). Also, due to the short runway at FLR, the landing may be a bit rough. So hold on to the seat in front of you, because the pilot has to break hard immediately after touch down, and occasionally you might hit the nose in the seat in front of you if you are not prepared for the ensuing whiplash.