Car rental

My advice would be to find a rental agency near a train station in a smaller town away from Florence. Many people also will go out to the airport and rent a car from there. The concerns would be of course traffic in Florence, but also the many ZTLs florence has. Some other advice, related to ZTLs would be when coming to a town in the area, if just passing through, look for a route around it, or if visiting, fins a lot on the outskirts and walk or take the bus into town. If you ask what a ZTL is, do some searching on this site or just an internet search.

thanks for the info. Outside of town was my first thought. But really sure what is the best place to rent. We are going to drive thru Tuscany and hard to Rome.

Rent from any company you wish-City center location. All rental companies in the city center are on via Borgognissanti or via Finiguerra. Exit the station on the right (Bar Deanna side). Go around the bar Deanna on via Santa Caterina da Siena (Sita bus station), cross via della Scala and walk to a small street called via dell'albero.
When the via dell'albero ends, the large street across via Palazzuolo, is via Finiguerra. The next intersection is with Borgognissanti. Go to the company you are renting from (they are all in those 2 streets). Pick up the car and drive west on via borgognissanti (it's a one way street, so no other option). Borgognissanti becomes via del Prato. When you see the Porta al Prato city gate in front of you, turn right onto the viale Fratelli Rosselli. Follow directions to wherever you want to go. There is no fear of ZTL on exiting the city center. Cameras are only on entry and in any case you won't go through any of those ZTL entry points.

Since your plan is Florence to Rome with a bit of Tuscany between. Look at a map and consider where Chiusi is. It is a major stop on the Train route between Florence and Rome. You could rent there, picking up and dropping off without much backtracking and avoiding airport and dropoff charges. Siena is close as well as many towns od interest. Another option would be Orvieto, still along the main train route, still do a pickup and return to the same location, but technically in Umbria, not Tuscany. You could still do a great drive from there in a day or two though.

Thanks for the advice everyone. This gives me something to think about. Having troulbe with this part of my trip planning. Nor really sure which towns/cites to spend the last half of our trip. This will help.