Florence and Hill Towns

You can't use a car in Florence. Cars are not allowed in the city center. If you rent a car to visit small towns in Tuscany, you should find a place out of town in Tuscany. Actually it might even make sense to visit Florence from there instead of staying in Florence. Just drive into the city and park outside the city center. If you intend to spend the last couple of nights in Florence, return the car in Florence before you check in, then go to Milan with the high speed train. Spend the last night in Milan before the flight, unless your flight is in the evening.

If you stay in Florence and rent the car there your rental agency will provide your car info to the authorities for permission to drive in the ZTL.

http://en.comune.fi.it/administration/mobility/florence_by_car.html

"Tourists that travel by car and who need to travel within the ZTL to reach their accommodation facilities or a garage can obtain a temporary access permit. In order to obtain this permit, communicate your licence plate number to your accommodation facility (or garage); they will forward it to the appropriate office. A temporary permit is issued for a maximum of 2 hours (for luggage transport purposes) only on arrival and departure dates. For the remainder of one’s stay clients have to park their car either outside the ZTL or in a commercial/hotel's private garage inside the ZTL."

We rented from the Hertz in the ZTL and returned it there at the end of the day - no problems.

You could stay in Florence for the 5 nights and day trip out to the hills - this would save changing hotels.

If you do decide to stay in Tuscany for a couple nights before Florence then definitely ditch the car and train into Florence.

It really depends on what you prefer and your comfort level of driving into the city of Florence.

Just remember, one wrong turn and you can expect a ticket.

I would stop in Volterra on your way to Florence. Volterra is really nice And I think it would be nice to spend one night there so as to have at least 1 and 1/2 day. There are also many small towns around Volterra, Pitigliano, Saturnia, Bolsena, Tuscania...which are well worth seeing.
However, if you do not know Siena And Florence, these two cities are must see.
I would go directly to Florence and spend as many nights as you can ( you would need a min of 3 days in Florence). I would do a day trip to Siena by bus, which takes you right to Siena centre. It is not so easy to drive in Siena. Siena is very nice and if you already know Florence, you might also decide to spend there 2 or 3 nights. To get back to Milan, it is however easier to do it from
Florence

I would visit hill towns for two nights -- maybe spent one night in a hotel in the historic center of Montepulciano (gorgeous city, fabulous views from its walls, tiny and walkable, and filled with good restaurants) and one in Siena (Hotel Athena and Palazo Ravizza are two hotels we have stayed in within the city walls with parking) and then drop the car at the Florence airport and take a cab to your hotel for 3 nights in Florence center. Never try driving into Florence even with directions from the rental company; that way has very high odds of landing you with a very expensive ticket or 2 or 3 if you stray into a bus lane or go around the block if lost.

Siena is worth most of a day and Montepulciano is IMHO the prettiest of the major hill towns. Here is a bird's eye view:
https://janettravels.wordpress.com/2011/09/18/climbing-the-torre-mangia-at-67/
Tuscany is worth much more time but when you have so little, I am personally a big fan of spending a little time in a couple of spots rather than rushing from one rather similar town to another scrambling for parking and figuring things out. These two stops with a little countryside viewing as you drive will give you a nice taste and a pleasant stop. You might stop at one other place on your way to Montepulciano and take the Chianti road to Florence and perhaps make a stop an Panzano or some other charming place on that drive.