We have rented cars in a city and at the airport. Yes, there may be an additional charge to pick up a car at the airport, however, it is a WHOLE lot easier. I am sure there is public transportation to the airport. Rental car locations in, or even on the outskirts, of a city are hard to find and to get to unless you take a taxi. Unless, of course, there is an agency located in the Florence main train terminal. But then you still have to drive out of the city. I would recommend the airport. As others have mentioned, you could drop the car off in Orvieto. Again, you have to find the rental car agency in the city which is down below the hilltown and might not be that easy to find. We drove around in circles for a half hour just trying to find the free parking lot at the Orvieto train station--and there were 3 of us looking. The other option would be to drop it off at the Rome airport and take the train into the city. It's really a toss up. If you get a GPS, it would make everything a lot easier. Last year, we rented from AutoEurope and had our own GPS for the hilltowns. It's easy to get lost on the red roads in Tuscany and Umbria. Before you leave, use www.mappy.com to find out exactly where the car agency, the hotel, etc. are located. Also, use this website to print out your train schedules. That way you know what your options are. Have fun making memories!