Renting a car in Florence

I rented a car from Hertz' city location at 53 Via del Sansovino. It was a 2 mile taxi ride from the train station. They gave me good directions across town without getting near any ZTL's, and the drive down to the Poggibonsi area was a breeze. It's just not very far down to Chianti and some of the hill towns like Certaldo and San Gimignano.
Sansovino was a medium size Hertz operation, and they had sufficient cars for my needs. I would think the airport would have a better selection of cars with more inventory available. We turned our car in at Orvieto and took a train into Rome--no drop off charges.
I suggest checking Hertz.com for rates, and then contracting AutoEurope.com to see if their rates are better. Sometimes they are. If you first join Hertz' frequent renter program (for free), you can sometimes get better prices or free upgrade to a class higher auto.

A fair amount of central Florence is subject to severe traffic restrictions which you might want to check with the rental service if you intend to drive inside the city.

Hertz has 3 locations in Florence: Airport, Borgognissanti, via Sansovino.
If you are staying in Florence city center walking distance from Borgognissanti, you should pick up there. You need to go there with your luggage if your hotel is located in a pedestrianized area, because you won't be able to drive back to the hotel to pick it up. To get out of Borgognissanti is very easy. Go straight west on Borgognissanti > via il Prato (it's one way, therefore no other choice). Then, at the ancient "il Prato" city wall gate tower, turn right on Viale Rosselli (it's a right turn only) then move immediate to left lanes and turn around the little park (like a U turn) to take Viale Rosselli on the opposite direction. Then proceed on Viale Rosselli going toward the river, pass under the underpass, then the blvd leads you on Ponte alla Vittoria (bridge) across the Arno. Follow the green sign directions to Autostrade (to right). Keep following the green signs. Eventually viale Talenti will turn into a divided freeway (to Pisa). But You will look for the A1 freeway to Roma. At the junction enter the Autostrada (the entrance is called Firenze Scandicci) pick up the ticket at the toll booth. Follow directions to Rome. But you exit at the very next exit (Firenze Impruneta). Pay toll at the booth, then look for directions to Siena. Take freeway to Siena and visit your hill towns. For SanGimignano exit at Poggibonsi.
Follow the above instructions on Google maps and street view to become familiar. There are no chances of been fined for the ZTL with the above itinerary.
If you take a taxi from the hotel to hertz you could also go to the Via del Sansovino location. It's along the itinerary I gave you. Basically shortly after you cross the bridge on the river (Ponte alla Vittoria) along the directions to the Autostrada.

I followed Roberto's directions , on a saturday morning last may from downtown Florence, very easy .