Best central Italy small town day trip?

My votes would be for Assisi or Orvieto - lots of things to see and do in both places.

Siena would be an easy daytrip from Florence, and you could stop in Or ieto on your way to Rome (check luggage at the Orvieto station), and fit in Assisi as well.

Siena is seen best as a day trip from Florence on the bus. We really liked Orvieto, and the train trip is about 70 minutes into Rome. If you're there early, you can catch a local bus out to Civita.
Or you can rent a car for a day in Orvieto to see the region.

If this is your first time to Rome, you're going to need all three nights there, so don't plan to do any daytrips during that time. Florence is your best bet for a daytrip, and I second the idea of Assisi. Here are some photos from our trip to Assisi, in case you're interested: Assisi in May 2008 Because there will be lots of other daytrippers there, get there as early as you can and stay as late as you can.

All of the cities you listed, as well as plenty of others (Lucca, Pisa, San Gimignano) are "favorites" of lots of people, and "second-rate" to others (or at least, second rate to Rome and Florence). So, unfortunately, you have to research yourself and see what appeals to you. I agree that you will need all 3 of your Rome days for Rome, so you should look for daytrips possible from Florence. I much preferred Lucca to Siena, but others feel the exact opposite.

I also agree you need the 3 full days in Rome, but if you want an easy day trip out of Rome try Trevi or Ostica Antica. Both are not far from the city and only need take a half day. Day trips from Florence, Lucca is sublime and not touristy by Italian standards , better still it is only an hour either by train or bus. Don't miss it, it;s a lovely place.

Thanks for all of the suggestions everyone! it's my second time to Rome but my husband's first as an adult, so we will likely want to see all the top spots. Going to compare all your options and make a decision on itinerary this week - thanks again!