Good base town for visiting Tuscany

Rent a car in Rome or Orvieto (if Orvieto is also part of your itinerary). Only Hertz has an office in Orvieto however.
Drive up to Tuscany from there.
Find a base location anywhere between Siena and Poggibonsi (however Siena itself has traffic restrictions, so stay in a hotel outside).
Then go to Florence and return the car on arrival.

While in Florence for a week you can visit any or all of the following:
Lucca, Pisa, Arezzo, Pistoia, by train.
Fiesole by city bus (no. 7).
Potentially Siena can be visited from Florence via Bus or train, however if you are staying near there the previous week, you might choose to visit it then.

We have been in Tuscany several times. I am always amazed at how small such an area is, in relation to North American concept of distance. Decide which cities you wish to visit and simply chose a city in the middle. If you have a car the city you stay in is irrelevant. Keep in mind cities and cars do not mix. We have stayed in Chuisi, San Giminagno, and Orvieto.

Have a great time.

As always, Roberto knows best. The train ride from Rome Termini up to Orvieto is 70 minutes. The Hertz office is just across the street from the Orvieto train station. You can make reservations at Hertz.com, and you can get a discount if you're a member of their frequent renter program or Gold Club. You can also compare Hertz rental car rates on AutoEurope.com, as you'd be getting a Hertz car if you rented there. Choose the cheaper reservation system. You can turn the car in on Sansovino in Florence which is about 2 mi. from the train station. CDW is required in Italy, but beware that they'll try to stiff you on personal property theft insurance--a racket.
We stayed outside Certaldo--and close to San Gimignano at a farm apartment I found on Booking.com. Virtually every farm in Tuscany has apartments and/or rooms for rent as secondary sources of income since their farms are so small. It was just over 90 minutes drive by toll road motorway up there from Certaldo. And Florence is maybe 30 minutes drive on 4 lane highways.
Our favorite hilltowns were Certaldo, Volterra and San Gimignano. Siena at night is also magical, but it's best visited by bus from Florence--across the street from the train station and beside McDonald's restaurant.

Karla, if you have not been to Orvieto, I would certainly start your Tuscany stage there, although Orvieto is actually in the neighboring province of Umbria. It is a lovely hill town, with lots to see and do, a magnificent Duomo, especially the facade, and some excellent restaurants, wine and shopping, such as ceramics and olive wood. You could take the train from Rome, just 70 minutes as mentioned, stay a couple of nights in the old hill town of Orvieto (via quick funicular from the train station), then pick up your car as you leave. You don't say what month you're traveling in, but if it is during the heat of summer especially, you could find an agriturismo with a pool, on the outskirts of a lovely and central Tuscan hilltown. Others in this forum can steer you better, as I myself have not yet done that.

We just returned from spending a week in Tuscany. We stayed at Castillo di Verrazzano, which is 5 minutes north of Greve. You could either stay at Verrazzono, which I highly recommend, or stay in Greve where you could walk to restaurants.

Greve is a nice quiet village, 18km south of Florence. Since it is not a hill town like Volterra or Siena, there's no ZTL to worry about. They have a large public lot with free parking. There are plenty of places to eat there.

All the Tuscany sights are 1 1/2 hours or less drive from Greve. Siena is ~50 minutes by way of a gorgeous drive. The charming hill town of Radda is 20 minutes away. Volterra and San Gimignano are 1 hour and 1 1/2 hours away. We did both towns in one day. If you are a movie fan, you can visit the estate in Greve where Kenneth Branaugh's "Much Ado About Nothing" was filmed.

Pisa, Lucca and Assisi are doable, but they are 2-2 1/2 hours away. We had plans to go, but ran out of time and scratched them from the itinerary.

We spent 8 days in Tuscany using Montecatini Terme as our base. It was well located for day trips to Volterra, San Gimignano, Prato, Pistoia, Cortona, Arezzo. We also visited Florence, Siena, Lucca, and Pisa from there but you will probably do those when you stay in Florence. It was a long time ago and I'm not sure how easy it is with a car these days but it's worth checking into. It's a lovely town with lots of restaurants and nice to stroll in the evening and, of course there's the spas you can spend a day enjoying. You can also visit the old town above it Montecatini Alto.

Or consider Montepulciano as your Tuscan base town. It's a lovely hill town with wonderful restaurants, cafes, wine shops and artisans, and extremely well-situated to use for day trips. Two of us used it as our home base for a week of Tuscan day trips, several years ago, and I plan to do so again summer 2016. Once you figure out how to get in and out of town, the first time, it will be easy (ask your host or hotelier for very specific directions). I stayed (and will be staying) at the beautiful, very well-priced "Politian Apartments" at the top of town (which have arranged parking for cars very near by, with validation for the ZTL zone). Yep, rent your car in Orvieto and then its a little over an hour's drive to Montepulciano. In "Italy 2016," RS describes M. in much detail and also offers a description of a great day trip through part of the surrounding area.

I think part of it depends on where you want to focus -- staying up near Siena is further north. We stayed at an agriturismo outside Pienza and it was about the middle of the area, so we were able to get to quite a few towns as day trip and hit others to Rome and coming out of Florence that were further away. The upside to the cities is that there's more to do/more restaurants, etc., but some of the hill towns are quite congested to get in/out of (esp. on weekends), so we were glad that we were a little more remote. As for the car, since we did the opposite route, we rented ours in Florence and dropped it in Rome, as it was cheaper than the outer cities and training in/out (like Siena or Orvieto). Plus, the hours were more limited.

I agree with jmauldinuu. Montepulciano is a wonderful hill town. I would stay in the historical old section on top of the hill. Hotel Duomo ( Hotel Montepulciano) or Camere Bella Vista are both great. They both have parking available. You take the train from Florence to Chuisi and rent car there. Car rental is right across the street from train station. 30 minute ride. Then return it there and train back to Florence for trip home. Day trip to Pienza and Montacino, Cortona, and others.

agree with Doug, Greve in Chianti is pretty much smack dab in the middle of Tuscany and a great base. Charming town.

My husband and I have done this a few ways: stayed in Siena in an apartment, stayed between Siena and Florence in a B&B in a rural area, stayed in Florence. Our favorite trips were in that order. Staying in Siena was by far our absolute favorite as we visited hill towns during the day and parked our car in the afternoon, had a fabulous dinner, then had Brunello and desert on the Campo every night for a week. No driving. We rented an apartment and they told us what parking deck to use. It was just outside the walls. We also used the train station parking deck and took the escalator across the street into town (note most folks here don't know its been operational for 5 years :)