First Time in Italy - Final Itinerary

Venice - 5 nights to allow time for day trips to Padua or Verona and Murano / Burano.
Florence - 5 nights also in order to do day trips.
Somewhere in Tuscany 2 nights.
Rome - 5 nights.

The reason for making this suggestion is to eliminate as much "lost" time as possible moving from one location to another. Even with the above you will lose at least three quarters (if not all) of three days in transit. It is really surprising how much time that actually takes.

I like your itinerary. Four nights in Venice to start is perfect, IMO, but you'll want to go back. Five nights in Rome is a minimum, but a good target for a first visit. You certainly could spend four or five nights -- with a car -- in rural Tuscany. Maybe find an agriturismo for a non-city experience. Depends on how much time you want to spend in the museums of Florence. That might be a snooze-fest for the kids unless they are art fiends.

Train from Venice to Florence, car for the Tuscany portion, drop the car in Orvieto to travel into Rome by train.

That looks good to me. In my month in Italy last June, I spent five nights in Venice (my first destination - the extra day was nice for recovering from jet lag), four in Florence, and five in Rome. And, yes, some time in Tuscany between Florence and Rome is a great idea; I went to Lucca and the Cinque Terre in between those cities. I found five nights in Rome to be enough. Not enough to see everything, of course; my intention all along was to return to Rome in the future. But it was hot and crowded in Rome and I was pretty tired by the end of my time there.

I don't have any experience of quiet little towns in Tuscany, and do consider Umbria as well - not much difference between them, but one of our regulars, Priscilla, spent quite a bit of time doing just that in September and wrote detailed trip reports for each leg of her journey. I recommend your reading them. Here's a link to one of them, you can find the others by clicking on her name and then on "view topics . . . . participated in" and find the ones she authored in September and since.

If you aren't especially interested in Renaissance art and architecture, consider spending 3-4 nights in Bologna instead and daytripping to nearby towns - Padua, Modena, Ferrara, Ravenna . . . . It won't be as crowded (or expensive).

Thank you all so much. We've decided to spend four nights in Tuscany.