Italy Itinerary

Why are you going to the Florence airport? If you don't already have your rental car, you should arrange through www.autoeurope.com to pick up a car in Florence proper. Airport rentals are always the most expensive, and inconvenient for the rest of your itinerary.

You have not said if you've purchased your flights. If not, it'd be more efficient if you flew into Pisa and out of Rome FCO. You want to minimize expensive backtracking and minimize train usage when possible. Upon your arrival in Pisa, take the airport train to the Pisa train station. Transfer to a train going to La Spezia where you'll take a short local train to Cinque Terre. When leaving the C/T, take a local train to La Spezia and transfer to a train going to Florence. Then spend your time in Florence. As you leave Florence, pickup your rental car at one of the city rental locations (not the airport). If you go thru AutoEurope.com, you'll probably get a Hertz rental there. Keep the rental car while touring Tuscany, and turn it in at Hertz, across from the Orvieto train station. While you're there, tour Orvieto, a popular hill town. Take the 70 minute train ride into Rome, and spend your tourist time there.
From Rome Termini, it's a 20 minute Leonardo Express ride to Roma FCO airport.

Thank you for your information. We already purchased our round trip air from Philadelphia, PA to Rome. We have reservations in Rome and in Florence already as well. I had read on another post to get a rental car outside of Florence by the airport to avoid getting a fine for driving in the wrong areas. Is it impractical to go to Cinque Terre and Tuscany?
Thanks again!

I like David's itinerary. You could train straight to the C/T from Rome. Then you'd have the car for Tuscany (and Orvieto is a great idea for a day). You won't want a car in the CT or in Florence. Or without Orvieto, you should be able to pick up a car not far from the CT, tour Tuscany and drop the car when you get to Florence. Usually the rental agencies are outside the TZL zones, but closer than the airport. Then taxi to your hotel.

Picking up the rental car at the Florence Airport is actually a good idea vs. the other recommendations to pick it up in the city. Here's why: It is VERY easy to accidentally get into the areas of restricted traffic in Florence, you won't know it when it happens, but you'll get a nasty ticket a few months after you get home. Theoretically, rental cars rented within the zone have fee passage out/back, however there are many postings on this and other travel sights with surprise tickets for cars that should have been exempt. By picking up at the airport you are far outside this controlled zone, and can get in and out of the Florence area easily. HOWEVER: you will have a short taxi ride or bus ride to get you from where you drop the car at the airport to the train station. Buon viaggio