Hill Towns

No. It is always better to choose one base and day trip from there. The process of changing accommodations with packing, unpacking, checking in and out is a time waster. Step one. Mark on a map the towns you want to visit during those two days. Step two. Choose accommodations that are central to those locations preferably close to one of the main highways, such as the freeway connecting Florence to Siena, or near the freeway connecting Siena to Perugia, if you choose to visit towns in Umbria and Eastern Tuscany.
Use those accommodations as a hub for your day trips. From near Siena for example you can drive almost anywhere in Tuscany or Umbria in 90 minutes or less.

I think it also depends on where you need to wind up and what you want to do while you're there. If you need to get back to Florence, then Orvieto is somewhat further away and you need to consider if you'd want to spend that much time on the road (we stopped in it on our way to Rome). If you want to go wine tasting, then Montalcino is great but if you're looking for just a cute hill town, then you may want to also consider Montepulciano or Siena or Cortona because there's more to see/do.

Dropping the car off in Orvieto makes me assume you're going to be getting on the train into Rome Termini. Orvieto is a great place to spend the night with accommodations of all prices. I like Orvieto, San Gimignano and Volterra for day visits. Siena is a great place to stroll around early p.m.
It's a shame that you don't have more days to spend out in the countryside. We stayed outside Certraldo 5 nights last year visiting other hilltowns.

Thanks for the responses. We are picking the car up in Florence and dropping off in Orvieto, and yes, the plan is to catch a train to Rome Termini. It appears that of the popular hill towns, Montepulciano might be our best bet. We're not that into wine and I haven't found a place to stay in Montalcino yet. I do have Hotel Corso booked in Orvieto. CM