One way car rental

Orvieto is a popular place to return Hertz rental cars because their office is across the street from the front door of the Orvieto train station. It takes 70 minutes to get into Rome Termini on the train. You can pick up the Hertz car on Sansovino, about 2 miles from the Florence train station. Pick a car up at any airport and you'll pay a bunch of taxes/service charges. We shop AutoEurope and Hertz' websites--choosing the lowest rate.

In Florence, renting a car at the airport and then driving out of town will work; however, having a rental car can be a significant problem (parking, traffic, etc) if you are sleeping in the Florence historic center.

One-way car rentals within Italy generally work OK, without drop fees.

You may already be aware of this but if not, It's important to note that for driving in Italy, each driver listed on the rental form must have the compulsory International Driver's Permit, which is used in conjunction with your home D.L. These are valid for one year, and easily obtained at any CAA/AAA office (two Passport-sized photos required, which may be provided by the issuing office). Failure to produce an IDP if requested can result in fines on the spot! Failure to pay the fines when requested may result in the rental car being impounded, and further charges for towing and storage. Have a look at https://it.usembassy.gov/u-s-citizen-services/local-resources-of-u-s-citizens/transportation-driving/ for more information on I.D.P's and driving in Italy.

You may also want to have a look at some of the other posts here concerning the dreaded Zona Traffico Limitato (limited traffic) areas that are becoming increasingly prevalent in many Italian towns & cities especially Florence, which is almost saturated with automated ZTL cameras. EACH PASS through one of the automated Cameras will result in a €100+ ticket, which you won't know about until several months after you return home! This website provides more information - http://www.slowtrav.com/italy/driving/traffic_cameras_speeding.htm

I've rented from Hertz in Orvieto twice. As of two years ago, the Hertz office is no longer directly across the street from the train station. It's now two short blocks away (unless they have moved again).

If you rent from Hertz, the most convenient location to pick up the car and head out south to Siena via the Chianti road is the Hertz location at Via Ambrosoli.
From there you take the Marco Polo expressway toward the A1 entrance (Firenze Sud). Just before the toll plaza veer to the right and follow directions to SIENA SR 222.

We rented from Hertz, but picked up and dropped off in Rome.

I suggest you double check to make sure there aren't any drop off fees. If there are, it might be better to plan a loop trip through Tuscany, then take the train from Florence to Orvieto. I'll leave it to you or others to do the research.

I think your idea is great! We spent 10 days in Tuscany using an agriturismo as home base. We actually stayed at a winery, Castillo di Verrazzano. Their wine is terrific and their lunch food and wine tasting was a wonderful way to spend the afternoon.

From Verrazzano, which is just outside Greve, we made day trips to Siena, San Gimignano, Volterra, Radda and Florence. If you stay somewhere near Siena or even Greve, you can drop by the more southern towns like Montelcino or Montepulciano on the way to Orvieto.

Driving in Tuscany was a breeze. I studied up on the rules of the road before we left. I went to AAA and got the IDP. We chose to take the bus into Florence to avoid the traffic and ZTLs, but if you are picking up your car at the airport at the end of your stay there, that shouldn't be a problem.

Everywhere we went we found any ZTLs well marked. In hill towns, including Siena, anywhere within the walls is going to be ZTL. There's plenty of parking just outside the gates and you just walk into town. Assume all speed limits are strictly enforced and be aware of the extensive use of automatic traffic cameras. Just because you don't see a police car doesn't mean you won't be see, photographed and ticketed. On a few occasions the locals wanted to go faster than me. I just found the first possible turnoff and let them by. We usually exchanged friendly waves. The villages and countryside is so gorgeous I didn't want to go fast anyway!

If you've never been to Italy, prepare to fall in love! Renting a car is by far the best way to see Tuscany. We were able to explore areas far off the beaten path.