Pickup rental car at Florence Airport or Train Station for Siena and back

When we visited Florence, we picked up a rental car at Hertz on Sansovino--2 miles via taxi from the train station. They gave me directions out of town to avoid getting close to the ZTL's downtown. Renting cars at airports just about always come with additional taxes/tariffs that are very expensive.
Most travelers going to the center city of Siena will take a bus, as they'll drop you in the center city. (Siena's train station is on the outskirts of town.) The buses park around the corner from the McDonalds across the street from the Florence train station.
If staying within Siena, it might be best if you took the bus down there and picked up a rental car in Siena. We found the city very congested for autos, and parking very difficult to find.
If you're staying out in the suburbs where you will have parking, you could pickup the car in Florence and make the 45 minute drive down there.
Many driving to Rome will choose to stop at Orvieto and drop the car off at the Hertz location across the street from the train station. It's about a 70 minute train ride into Rome Termini. And Orvieto's a great hilltown and popular stop to make.

There are no rental offices at the station. They are all on Borgo Ognissanti, a street about 10 min walk from the station (about 20 min walk from where you are staying). I would rent from there or, if you happen to use Hertz, from the Hertz on Via Del Sansovino. You will definitely need a taxi to get there. The airport is not conveniently located for you and picking up at the airport means higher rental fees due to the airport taxes. If you pick up in the late morning hours you should incur in no significant traffic.
From Siena it makes no sense to back track to Florence to go to Rome. Just drive to Rome and return the car in Rome. Depending on the company you use I can give you the location to return it. You may not be able to drive to your hotel as traffic is restricted in large portions of that area of the historical center.

Thank you both for the great advice. I think I will rent from Hertz outside Florence at Via Del Sansovino. I have to return the car 3 days later on a Saturday and be in Rome on Saturday. Hertz in Orvieto closes at 12:30 on Saturday so looking at Hertz locations on the outskirts of Rome near a train station so I can take a train to my hotel in the center of Rome. Do you know of a Hertz location north of Rome with easy train access to my hotel.

Thank you both for the great advice. I think I will rent from Hertz outside Florence at Via Del Sansovino. I have to return the car 3 days later on a Saturday and be in Rome on Saturday. Hertz in Orvieto closes at 12:30 on Saturday so looking at Hertz locations on the outskirts of Rome near a train station so I can take a train to my hotel in the center of Rome. Do you know of a Hertz location north of Rome with easy train access to my hotel?

See if there's a Hertz drop near Tiburtina Rail station. That's very easy to get to from the autostrada from Tuscany. I'm thinking there should be plenty of trains going from there to Termini. We took a taxi from Tiburtina to our apartment near Piazza Navona. Think it was in the 50 euro range. Worth every one of them.

We're doing something similar (renting a car in Florence, going through Tuscany and then dropping off at Siena. When I booked, Hertz (online) told me that either the pick-up or drop-off of the car HAD to be at an airport location. Did you not get that same directive?

You can return it at the Tiburtina station or the Termini station. Both are easy to reach from the Tangenziale Est/A24 (you can see that freeway coming from the East of the city (check Google Maps).

Hertz also has a facility at the IKEA at the PORTA DI ROMA shopping center. That is very easy to reach coming from the A1 from the north. Just follow the directions to the CENTRO COMMERCIALE/VIA BUFALOTTA. Then you will see the IKEA signs all over. That office is open every day Mon-Sun, from 8 to 9pm). No matter which drop off location you choose, then take a taxi to your hotel. Unless you return it at the termini station and your hotel is within walking distance. The return location for the Termini station is actually inside the parking structure at the Radisson Blu Hotel. The entrance to the parking structure is at the corner of Via Giolitti and Via Mamiani (check Google Maps for directions). I usually return my rentals in Rome here. It's not difficult coming from the Tang. est/A24.

If you return the car on a Saturday afternoon, the stations' offices and the IKEA Porta di Roma office are few of the ones open. There are no locations that are open on weekends between Florence and Rome. The Siena office is also closed on weekends after 12:30pm on sat. Also coming via train from Siena is a hassle anyway, because you need to take the bus back to Florence and then the train from there.