advice on travel plans :)

A car is good for Umbria and for Tuscan hill towns. Why not spend a couple of days seeing Florence on foot, then rent it for a day (or two) or Tuscan day trips? (We did a similar pattern in Siena a few years ago.) I have not parked Florence, but here is an article describing options. It is a terrific city to explore on foot! Then keep the car for Umbria. It might be fun to stay in an agriturismo in Umbria where parking is not a problem.

My question is, where are you renting the car? If in Italy, then driving to Nice and back, then you'll be OK. If in France, international drop off charges are huge. Also the dreaded ZTL's are a threat, and theft of/from parked cars is not unheard of in Italy (or the US for that matter).

I should have provided more info! We are planning to rent the car in Nice and use it to do day trips from Villefranche-sur-Mer and then drive to Florence - thinking we would need to park it there for two or three days - and then drive on through Umbria/hill towns and then to Rome. Bad idea? Two years ago we rented a car in Paris and dropped it off in Amsterdam (went to Venice, Germany, etc.) and it did not seem overly expensive. But I could be missing something?

Thanks, Laurel, for the link to parking options in Florence. I'm starting to think we should drop the rental off there and then pick up another rental car up after three nights in Florence. We'll have to check the cost of that option...

Just saying confirm the drop off fees and be sure you can live them and no nasty surprises. The rail options from Nice to Florence are not that good. The fastest way is to Ventamiglia than change to an IC train to Milan, then a fast Freccia train to Florence. 7 hours all told and kind of a round about way, but the more direct route along the coast is slower and the trains not as comfortable. I'd also consider dropping the car in Nice, taking a train to Genoa and renting a car there. Again, depends on drop off fees. The ride along the coast can be quite stunning.

You can drop the rental car at the Nice airport, and you fly really cheap on EasyJet.com to Venice. At $9.50 per U.S. gallon in Italy, I try to minimize going long distances by auto.
Visit Venice, and then a fast train to Florence is about 2 hrs.

Pick up a rental car in a city location as you leave Florence for points south--Tuscany and Chianti. I would suggest seeing Siana, San Gimignano and Volterra at a minimum.
Turn the rental car in at Orvieto train station (Hertz) and take a train into Rome. Orvieto is another very popular hill top town with great B&B's and hotels.

We made all these stops on our last Italian trip, and really enjoyed our 6th trip to Venice, if just for one day.

We once did a similar trip. Arrival and car rental pick-up in Nice, stayed a few days in Villefranche-sur-Mer, then drove to Cinque Terre (although the drive down to Vernazza was somewhat unnerving) and parked it there for a few days, then drove to Sienna for a few days (day trips to Florence and Tuscany hill towns) and finally drove to the Rome airport where we dropped the rental car and then took the train into Rome for our last few days. The drop-off fee for the rental car can be a few hundred dollars, but overall I think it can be time and cost effective. In Florence, I think you can drive into and park in the city center if you have a hotel reservation in the center; otherwise you need to avoid driving into the center. For our day trip there from Sienna, we parked outside the center and just walked in -- very easy. Personally, I always travel in Europe with a rental car, to have the most flexibility and freedom -- plus I enjoy driving in Europe. Drive carefully, avoid speeding (and the speed-radar cameras), and don't leave anything visible in your car that would tempt a break-in.

Marie, you commented "Two years ago we rented a car in Paris and dropped it off in Amsterdam (went to Venice, Germany, etc.) and it did not seem overly expensive." That sounds like quite a trip and I'd like to hear more about it! In any case, do you recall what the drop-off fee was? We have a trip planned this year for Paris, then car rental pick-up and drive to Normandy coast, then Belgium, then Amsterdam (car rental drop-off there). The drop-off fee quoted by Sixt is a few hundred dollars but I think it is still cost-effective.

As far as the hotel registering your car for ZTL permit, there have been posts from people who thought the hotel registered them and got home to find huge fines for numerous ZTL violations in their mailbox. It is hard to fight city hall from home in the States. Turns out they did not have the right documents signed by the right official, and could not prove it. The hotel said "We know nothing." If you live in Florence, and your cousin has a best friend that is special assistant to the deputy commissioner of street lighting, that is one thing. Otherwise, you are just another rich American tourist, so pay up.

I'd keep it simple - for all the reasons already explained. Fly from Nice to Italy. Get to Florence by train for a couple of days, then rent a car in Florence and stay at an agriturismo in Tuscany for the remainder. Return the car in Florence and take the train to Rome.

As for Florence, if you love Renaissance art and architecture, 3 days is a minimum. If you just want to see the highlights, a day is enough. There are other Tuscan towns with more atmosphere and charm.

Renting a car in France and dropping it off in Italy may result in INTERNATIONAL DROP OFF CHARGES OF UP TO €600 (US$800).
You must inquire with the rental car company you will use what the drop off charges are before you attempt your plan.
If the drop off charges are high, as often are, you have the following alternatives.
1- drop off car in Nice. Take a train from Nice to Italy. Sanremo and Genoa have major rental car companies. Proceed to Tuscany by car. You won't need a car in Florence. Choose this option only if you intend to stay outside of Florence to visit Tuscan cities and towns, including Florence, from that out of city location.
2. drop the car off at Nice airport. Fly from Nice to Rome (Easyjet). Visit Rome first, then take train to Florence, visit Florence. Fly back to NorthAmerica from Florence (via one of the major EU hubs). This option requires no rental car in Italy.
3. Return car in Nice. Take train from Nice to Florence. It's a long 8-9 trip with train changes (at Ventimiglia, Genoa and Pisa). Unfortunately the Nice to Florence rail option is not fast since several sections between Ventimiglia and Genoa are single track. However the coastal rail route from Nice to La Spezia is one the most scenic on Earth, therefore your time on the train will be well spent. You will pass through the Cinque Terre too.
The Ventimiglia to Milan to Florence route (changes in Ventimiglia and Milan Central) may be faster (7 hrs only), however not as scenic.

Thanks for all of the advice! It is very much appreciated. It's obvious that we will have to do some thinking about how to handle this itinerary most efficiently (and cost effectively). Your advice is priceless. We don't really want to go to Venice again - would really like to take the car from Nice all the way to Rome - so it might make sense to do Florence as day trips from Sienna (or elsewhere) as recommended by Roger (and Roberto). But we will also consider that long, slow train ride from Nice to Florence through Cinque Terre...
If you come up with any other options (particularly the car problem in Florence), let me know. Thanks again!
PS to Roger regarding our car trip from Paris to Venice through Germany and dropping off at Amsterdam two years ago. The cost was about $800 USD total, including a 200 euro drop off fee. It was a 6 day rental. We, of course, had to pay to park the car in Venice. I thought the cost was not too bad, really. Stayed in Geneva one night (to see the Hadron Super Collider - physics-nerd son - plus they had just discovered the Higgs boson). Then three nights in Venice, two in Rothenburg, two in Amsterdam (dropped the car off there the first day).

Sanremo is not far from Nice. Avis rent a car is in Sanremo. Maggiore rent a Car (the largest rental car company in Italy) also has an office in Sanremo (www.maggiore.it).
Genoa has many more car rental companies, however it's a longer train trip.

Agree with Roberto,`drop the car in Nice @ train station, train to Sanremo. We took a taxi to the rental place.
If I remember correctly, it's the first stop after Ventimeglia. We did this several years ago, and the drive is beautiful. Think it took us 4 hours to Lucca.