Do not try to drive in Rome. Drop at Orvieto and train into Rome. This may also help:

DRIVING IN ITALY & SOUTHERN EUROPE

Q. SHOULD WE DRIVE IN ITALY?
A. Of course you should if your driving skill & confidence would allow you to drive a rental car in Vermont, Colorado or California. But, be advised of these tips:
* Avoid driving in the major cities except for picking up or dropping cars
* Have good maps—study them in advance—and have a GOOD NAVIGATOR.
* Stay in the right lane except when passing and use your rear view mirrors

Q. WHAT CAR SHOULD I GET AND WHERE DO I GET IT?
A. It is best to rent your car before you leave for Europe. The best source we have found is www.autoeurope.com [800-223-5555] who is a broker for several car vendors. They will quote you prices to include the variables that are often omitted by others, such as unlimited mileage, mandatory insurance coverage with some deductibles, and VAT taxes. It is wise to compare prices and coverage with their sister company at www.kemwel.com. Autoeurope will match any comparable quote, and are famous for their customer satisfaction if problems do arise with the vendor. The best model will depend on your needs, but for best value we suggest you select a compact car with manual transmission. Automatics are available but will cost you about 30% more and may limit your model options & pick up locations.

Q. ARE ITALIAN DRIVERS AS CRAZY AS I HAVE HEARD?
A. Yes & no! They are certainly aggressive, but they are also more skilled than many USA drivers—both are a function of necessity. Italy is one of the most crowded countries in the world and the drivers have evolved these characteristics
* They are notorious tailgaters. If that bothers you, pull over and let them past.
* On the AUTOSTRADE they will drive fast, but will stay in the right lane except when passing and will use their blinkers when passing—YOU SHOULD TOO !
* They will often pass on 2-lane roads with traffic coming. Frankly, they expect you, and the oncoming car, to adjust to the shoulder and make 3 lanes of traffic.

OTHER ROAD TIPS FOR YOUR DRIVING SANITY:
1. Learn the meaning of the sign “ SENSO UNICO” and take heed [ONE WAY ].
2. Be sure to get your ticket when you enter the AUTOSTADA system & be prepared to pay the toll when you exit it [ rule of thumb—300 km=15 Euro]. You can use your credit card in the VIA lane at the toll both, or buy a debit VIACARD in advance.
3. Do NOT attempt to follow road numbers—that will frustrate you. But, do pay attention to the directional signs that point to your destination [ TO MONTALCINO]. And, be aware if that road leads eventually to a larger city [ ROMA—SIENA ETC.]
4. Unless you have a diesel car, you will want to fill the tank with benzina from the green pump. Most stations will pump gas for you and will take credit cards.

NOTE: As of 2005, an International Drivers Permit[IDP] is required in Italy.
You can obtain them from your local AAA office. You will need a valid US driver’s license, two passport photos, and $15. The photos can be taken at the AAA office.

I completely agree w/Bob; If planning to be in Rome for a while DO NOT drive in Rome. Train is soooo easy.

The train from Florence to Rome takes 1.5 hours. Why would you spend twice the time (getting and returning the car and driving to Rome) and more money to rent a car. Take the train!

It looks like the OP plans to take three days to drive from Florence to Rome.

I had planned to take a day trip to Pisa, then had a wine tour at Fattoria di Fèlsina (owned by friends of a friend), just south of Florence. Then spend a day leisurely drive to Rome. I plan on dropping off the car as soon as we get to Rome.

thats correct ellenem. by way of Pisa and Fattoria di Fèlsina.

I would agree if you're not experienced driving in Italian cities, then I'd stay out of Rome. It can be a little challenging. You can drop your car at Orvieto, Chiusi, Viterbo or the outskirts of Rome and catch a train/bus into the city. This link has 200+ rental locations in Rome and those other cities -- including maps!

http://tinyurl.com/car-rome