Those 4 places are easy driving distance from each other. Italy has beautiful countryside and I would definitely recommend driving. The only difficult part is parking in the city, but if you stay in a nice hotel with parking you'll be OK.

You might think about flying into Milan. From the airport there, it's a short drive to Lake Como which is a good place to get over your jet lag. From Como, you can drive to Venice. From there go to Florence. Rome is about 2 hours south of Rome.

Then you can fly out of Rome, or drive back up to Milan. If you drive back up, you can take the eastern hill route and stop by Assisi.

I might recommend visiting either Capri or Ponza depending on the time of year. Or take your car on ferry to Sicily and visit Corleone.

I have an excellent road map of Italy if you need help, or I'm sure you can buy one at a bookstore.