Umbria

This depends on what mode of transporation you will be using, and what you want to see. We just got back. We decided that we wanted to use a car, so we could stop anywhere, at any time. We also wanted to be close to the freeway(A1, so we could go North and South quickly, before we branched out East and West. And we wanted to stay at an Agritourisimo, one with a self-contained apt, but be close to a town with lots of dining options. We chose an Agri just outside Orvieto. Orvieto was an easy drive from Rome, or an easy train trip. We jumped in the car each day and explored all of the area, from Montalcino in the North West to Assisi in the East.

"best" is a trouble-causing word; I suggest searching for several good options rather than stressing over finding the one location better than any others. As for specific town suggestions, it would help if you say whether you have a car or not, and what you are looking to visit (hilltowns, wineries, etc)

We really liked Orvieto.

with a car you'll have lots of options; you can stay in a hilltown and park either in the walls or on the road just outside, you can stay at a place in the country, you could stay in a larger town. Just go thru a guidebook and figure out what you want to do, then pick a location somewhat central to it. We've stayed in a variety of hilltowns and enjoy it because at nite when the hordes of tourists are gone it feels like you've gone back to the Middle Ages. The region isn't that big, so it isn't as if you can go wrong no matter where you stay (except for staying in Florence, which has the dreaded ZTL's).