We will be in italy for 10 full days in April, 2 adults 2 older teens. We will fly into Venice and out of Rome. We’d like to see some areas in Tuscany and Florence and Spend the Last day in Rome (we’ve been there before). We want to drive some of the trip if not the whole thing. We are not opposed to doing a train for a section of the trip. Where do you recommend we stop, drive, stop? Thanks for your recommendations.
The car will only be of any use in rural Tuscany. Decide how many days you wish to devote to Venice and Florence, plus deduct the 1-2 nights for Rome to see what you have to work with. No reason to not take a fast train to Florence and pick up the car as you leave town. Up to you whether to drop in Rome though--will depend on your itinerary.
Since driving in Rome would be a nightmare, your drop off plan is crucial. Many posters here drop off at the airport and stay at the on-airport Hilton. (Not saying you should do that, just a common solution here.)
I agree that the car is very useful in Tuscany, but useless (indeed, a hindrance) in Venice and Rome. Some posters here said they managed to park in Florence, but I wouldn't try it. We spent three nights in Florence without missing a car at all. Took the bus to Fiesole for an afternoon.
Perhaps it's easier in April, but in July, we had to search for parking spaces in the popular Tuscan hill town lots. Kind of like Christmas at the mall.
Are you already familiar with specific Italy problems, like IDP, ZTL, and government-required insurance that can affect your own plans for insurance? Every time I asked Garmin to take me to a particular outside-the-walls parking lot for Siena, it gave me a route right through the city and ZTLs!
Venice: 3 nights
Florence: 3 nights
Rent car in Florence (I gave instructions in separate posts on how to exit the city by car. Use the search engine to find it.
Drive to Tuscan rural/small town location of your choice. Stay there your remaining number of nights except for the last night (to be spent in Rome).
Drive to Rome.
Return car at Fiumicino Airport, stay there your last night. Or, if you prefer to stay downtown, return downtown.
I usually stay at the Rome Airport Hilton, connected to Terminals by pedestrian walkway, on the night before my flight. There are cheaper options near the airport, but then in the morning you might need to spend 20-30 euro by taxi unless the airport of your choice has a shuttle van to the terminals. Since you've been to Rome already, you might skip staying in the city altogether or visit it from the airport hotel (55 euro each way by taxi or 14 euro per person each way).
If you must absolutely spend your last night in the city, you could return the car at a downtown location. The traffic in Rome and the traffic restrictions in the ZTL (Limited Traffic Zone) make that option a bit more challenging but it is doable.
If you return the car at the Fiumicino airport, set your navigator from Tuscany to stop at this freeway Service Area to refuel your rental car.
https://maps.app.goo.gl/RwNJCBGhgPMQMzW97
Then, after refueling, set your navigator to the rental return at Rome airport.
https://maps.app.goo.gl/DxQTUwJLKHJ4bJP2A
I set the above to return at Avis/Budget, but there are 4 huge parking structures across the terminals: A, B, C, D.
Some rental return companies are in A, some in B, few in C. So pay attention to the signs. A will be on your left, B on your right. Choose the correct one based on the car company you use. Don't get distracted or you will have to go around the airport area again.
If you return the car downtown, the rental locations may vary (they are not all in one place, except for the Termini station which are all at the garage here:
https://maps.app.goo.gl/XEiP1nwnDP2ET2A57
But no matter where you choose to return the car downtown, in all cases I recommend you first stop at this freeway Service Area for refueling:
https://maps.app.goo.gl/71jT4AnBGA2DdWrb8
Then reset the navigator for the rental car return of your choice downtown.
The rental return locations near Tiburtina stations or Termini Stations are not difficult to reach and will be sufficiently far from the ZTL.
There could be also the option to return the car at Chiusi (in Tuscany) then take the train to Rome. That option is available only if you rent from Avis/Budget.
The Chiusi rental car agency is here:
https://maps.app.goo.gl/sxPdocPG5nzVSd5B9
Be aware it's a small franchise agency, so they close at lunch time, and close completely on Saturday afternoon and Sunday all day. You could also go there by train and pick up the car and return it there. As I said it is a small agency so their fleet may be limited if you are in need of a large van or an automatic car.
Just to add....
If you haven't reserved your accommodations yet, the clock is ticking: you really need to do that ASAP. I'm crossing fingers that you're not traveling over the Easter holiday?