Look at your flight options before deciding to fly out of Venice as many departures are very early morning.

It's not clear (to me anyway) exactly what your priority destinations are. Do you want to visit Florence? Milan? Or are you contemplating only Rome, Siena, the CT, and Venice?

Will it be closer to 10 days or 12 days? Even two days can make a difference when you're hoping to go to multiple destinations. Getting to the CT from anywhere will take a lot of time. By train, it's about 4 hours away from Florence or Milan and about 6 hours away from Venice. Faster if driving but having a car at either end is useless and expensive to park.

IMO, Siena is not a countryside spot to "regroup and relax." Orvieto or Lucca might be closer to what you had in mind. If you rented a car, you'd have many charming, smaller towns to choose from. Just to mention a few of the popular ones: Montepulciano, Pienza, San Quirico, Montalcino in southern Tuscany. Castellina and Radda in Chianti. Volterra. If you're heading to Venice after Rome (or vice versa), you could also consider stopping in Umbria. Spello, Bevagna or Todi, to name a few.

Thank you for your answer - priorities for daughter are Rome, Florence. Venice would be new for husband; CT new for me. Thinking that circling back to Rome would be time waster, so thought a flight out of Milan (direct to Baltimore) or from Venice (so can see Venice) would be wise. Maybe save CT for another time?

Well it is a short time and you lose half a day for every move. If I had ten days I might look at
Rome 2 days
Siena 1 day (not stay)
Florence 2 days
Venice 2 days (one day is just too small)

Chilling out towns are as Jean's list (i'd chose the same or even hotels with a pool in between) and a car. I think I'd take the train Rome to Florence and then just a car for the Siena and Venice part getting rid of the car at arrival in Venice.

June will not be crazy so should be a good trip

Flight departure times back to the states are usually better out of Rome or Milan (Venice flights usually depart very early). Since Milan isn't a priority, I would look at flying into Venice and home from Rome. Another option would be fly into Pisa and home from Rome. If you fly into Pisa (non-stop flights from NYC), you can transfer to CT on arrival. Unwind the first two nights, train to Florence (2-3 nights), train to Venice (3 nights), train to Rome for the remainder (needs at least 4 nights). Do you have 12 hotel nights in Italy?

Into Venice and out of Rome makes the post practical sense because of the flight time problems leaving Venice and for staying in one direction.

You probably need to consider something like this to realize all your trip wishes;

Venice 3 nights (jet lag wasted first day)
Train to CT - 2 nights
Train to Florence - 2 or 3 nights
Train to Rome 3 nights

With 4 places in 10-12 nights you don't' really have a need, or time, for a car to explore outside the cities, except.........you could rent a car leaving Venice and drive to CT (not that interesting along the way so do it straight), then visit a couple of Tuscan hill towns on your way to Florence (San Gimignano, Volterra) drop the car and train to Rome when finished. Still a bit rushed in the middle, though. If you were willing to substitute a 2 day Tuscan village stop as a relaxing substitute for the CT, it all starts to settle down a little.

I very much agree with Aramis' suggestions, including to skip the Cinque Terre this time and substitute it, if you want, with time in some Tuscan hill towns.

Figure out all of your general travel times (i.e., 5 hours, or whatever it is, to the Cinque Terre) to all of your possible destinations, sit down with DH and DD, and decide how much of your limited vacation time, and for which locations, you want to trade off travel time vs. "being-there" time.

And in terms of chilling out, for me, sitting in a piazza in Piazza Navona, Campo de'Fiori or by the Pantheon with a glass of wine is just as relaxing as being in the countryside!

Thank you all for your assistance. We are going to limit this trip to the three major cities, Rome, Florence and Venice, train only - no car. This way daughter will get a full experience of the cities and hopefully will have many more opportunities to revisit in the future.

There are some excellent day trip options from Florence - Siena or any number of other of the other hill towns (by bus usually). Just Google for day trips from Florence and include the own name if you have one in mind.

From Venice you could visit Padua, or even Verona.

Have fun.