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Car rental location from Rome

Help, please! I'll be spending a few days doing the major sites in Rome before renting a car to drive to Tuscany (Montepulciano area) and then will be returning the car in Florence. Based on what I've been reading, I'm getting nervous about driving out of Rome. What rental car location would be best for ease of driving out of the city area? I'm open to any rental car agency. Termini, Tiburtina, airport (FCO or CIA)? Would it be better to take a train from Rome and picking up a car in Chiusi?