We just returned from a wonderful 11 night Rome (4), Chianti agriturismo (4), and Florence (3) vacation with my wife and 2 teenaged boys. Everyone loved the whole experience which I planned using all the great information from this site. I just wanted to share some lessons learned about the rental car so others may benefit (sorry for the lengthy post)
1) We picked the car up at the Hertz office in Orvieto after taking the train from Rome. I reserved the car with a credit card that provides insurance for rental cars but it requires you to decline CDW/LDW. When I told the rental agent I wanted to decline their coverage, she told me she would need to put a hold on my credit card for the entire value of the car (16,000 Euros!). She tried to do this but the charge/hold was rejected since the card only had a $15k limit. I had several other credit cards with me but didn't like the idea of putting a ~$18,000 charge on my cards so told her I would take the CDW - it was about $90. So be aware you may need to put a large charge on your card(s) if you elect to use the credit card rental car insurance.
2) We rented a Tom-Tom GPS navigation device from Hertz. She only charged me 10 Euros a day rather than the normal higher price since she could tell I wasn't happy about the CDW situation. The GPS device was invaluable finding our way thru the small windy roads of Tuscany (we drove ~650 km over the 4 days). It was very easy to use and even had an audible alarm when approaching roadside speed cameras. This probably saved me about 8-10 speeding tickets because when it went off I was always going 20-30 kph faster than the posted speed that is displayed on the Tom-Tom. I highly recommend this device or another GPS navigation device with similar features.
3) It took an entire hour from the time I walked into the Hertz Orvieto office until we drove off in the car. Even though I am a Hertz gold member, the car wasn't ready - it had to be cleaned and washed. Not sure if this is typical but you may want to plan for this.
4) We dropped the car off the Florence Sansovino Hertz office which worked out great. Thanks to Ken (I believe) who suggested this location. The Hertz office called us a taxi which then took us on a short 10 min ride to our hotel in central Firenze (Pensione Pendini at the Piazza Republica)