Hope you are not planning on originating a car rental in Spain and drop it in Italy.
You will get crushed with one-way drop fee.
You've got 13 hours of driving on autoroutes the whole way.
Really impossible to answer your question without knowing what your interests are.
Do you want to oceanfront villages? Roman ruins in Western Provence?
Scenery wise the coast between St Raphael and Monaco via Nice is unbeatable. Without an answer to above detailed interests I would suggest Nice,Villefranche, Antibes or Cannes. Nice is the biggest town but still only a tenth the size of Barcelona, Villefranche is the most beautiful town, Antibes has the widest mix of ancient and modern and Cannes is ...well...Cannes.
Yes, we were planning on dropping the car off in Italy. How much do you think the surcharge would be? We want to drive to experience the little towns along the way. We will probably follow the route given by Via Michelin. Taking little side routes here and there to see interesting sights. If there are any towns along the way that are a must see we want to see them. We would like to see coastal towns and rural. We love wine tasting, old beautiful stone villages, etc. not really into big cities.
A possible alternative would be to cross the borders via train and then pick up and drop off a car in France, then another one in Italy.
Did you rent the car yet? Why don't you contact AutoEurope (US broker situated in Maine) and see what the drop off fee would be. Generally, it is pricey and, as dat noted above, for a good reason, since someone will have to travel to Florence to get your car back to Barcelona.
Sticking to one country is a much more practical way to go. At the very least, train from Barcelona (you do not need a car while in Barcelona) into France and pick up your rental there. France is so diverse and there is so much to see and do, that you could easily spend your entire holiday there and be very-very happy. However, if you are determined to continue to Italy, again, drop your French rental car at a point in France and than either train or fly to a point in Italy, where you can once again pick up an Italian car (completely different insurance requirements). However, if you are only visiting Florence, than you really do not need a car.
Perhaps give us some more info as to where you are in your planning, ie, is this a theoretical plan or was anything actually reserved and paid for (we would need to work around that); also what is it that you want to accomplish on your holiday: what do you want to see and do other than driving? Do come back.
Good advice from Anna....
The French Riviera is part of Provence.
Ok, so you will fly into Barcelona (no need for a car there) and fly home from Florence (no need for a car there either). You will need to make a call as to whether you want to spend the four remaining days in Western Provence (lovely small towns, perched villages, charming countryside, wine regions) or the Riviera (still Provence; still perched villages inland, but more coastal location). Four days is not enough to experience both. You could drive through the entire region but what will you accomplish in doing this other than stare our the window? Where you want to visit in France will be your call. One being better than the other is way too personal.
Let me ask you, since this may actually sway in one direction or another.. when is this dream trip planned for?
We are planning for next summer. Most likely end of June. We will have to think about western provence or riviera. We love small quaint villages and wine tasting, so maybe western provence. I just don't want to be taking so many trains and hauling luggage. Would it be cheaper/ less hassle to take the train from Barcelona to Avignon and rent a car in Avignon and drop off at the airport in Florence?