Hilltowns

For research and such, there's only one 's' in Siena. Half the people in the world make the same error - - don't feel bad. Well Ed, yes, there is only one "S" but there's also only one "n". :-) Mary: Less is more. Take your two days (one night?)and go to Orvieto, see Civita, maybe pop into Tivoli on your way back to Rome. The rest of the locations are just too much road time, IMHO. You won't see anything but road.

Since you only have two days to explore outside Rome and many of the places are on your wish list are hundreds of miles away may I offer another travel option. From Rome drive and hour and a half to Orvieto. Cathedral is stunning. Then head north. Lovely hill towns await. Small, quaint, endearing. One of the best meals I had in all of Italy was at La Grotta in Radicofani. No tourists but us in the place, no one spoke english, authentic family owned and operated restaurant. It was heaven. Owner came out of the kitchen with the plates of food. Very proud, very happy we ate everything put before us.
Divine food, divine. We also adored our stay Palazzo Palesa B & B in San Casciano dei Bagni. The icing on the cake on this Italian sojourn was the wine tasting in Montepulciano. Only a suggestion to get a feel of the Italian countryside of Southern Tuscany. Bella Italia. Bella. Enjoy your trip.

The whole loop (not including Tivoli which is close to Rome) is probably a bit more than five hundred miles with, at best, ten hours or actual road time. There's going to be a lot of hypnotizing freeway. I wouldn't want to tackle even half of it the day I hopped off a plane. Even if you survived it, there's just not enough daylight to spend a couple of hours in each spot - - and they all need at least half a day, even if you scurry. Eliminating Lucca, Pisa, and Volterra cuts the driving time by more than half and makes it workable - - barely. Tivoli is a separate project in another direction - - skip it, or go there one day and Orvieto the next and do nothing else. For research and such, there's only one 's' in Siena. Half the people in the world make the same error - - don't feel bad.

Thanks to everyone's speedy replies. Not the answers I wanted, but I quess I needed to hear it from experienced travellers. Does it matter that we have two full days and nights and don't need to be back to Rome until Sat. at 10am?

Peronally I would do two nights in Orvieto and add the rest to Rome. And FWIW, neither Pisa nor Lucca is a hilltown. They're both on flat plains. Happy travels.

Well, Pisa is a 3 and 1/2 hour drive from Rome. It is doable. Simply depends on how much time you wish to spend exploring the towns you listed. That seems to be the farthest spot. Then it's a half hour to Lucca, from Lucca back to Siena another two hours.. If you love road travel then go for it.
To make it happen and to answer your question about what to skip I'd leave Civita, Volterra, San Gimignano and Tivoli off the wish list. Also keep in mind what time of the year you're traveling. If after the first week of November the sun starts setting around 5pm. 4pm in December. Lastly, don't forget Italians enjoy a siesta time which means you could arrive somewhere at 1pm and find many shops, cafes, etc. closed. Whatever your final choices, enjoy La Dolce Vita.

For me the best part of any well known destinations for tourists such as I begins in late afternoon and lasts until mid morning when the day trippers return. I manage my day trips from base camp on that schedule. And my most important criterion for base camp ion is it's proximity to day trip worthy sites that fill a liesurely road (or train) trip for which I can depart in mid morning and return in late afternoon. I've done gonzo race horse road trips. I once drove from Berkeley to West LA as a day trip just eat a burrito heralded as CA's best. My current modus operandi is (are?) more fun and more rewarding.