Rental car Siena to Chiusi?

You would do best to drop the rental car off in Orvieto where the Hertz office is just across the street from the train station. Orvieto is on the motorway just over an hour north of Rome, and it is an especially popular hilltown. Most small cities in Tuscany and Umbria don't even have any car rental agencies.

Actually there is an Avis a block away from the train in Chiusi as well! But if it gives us a chance to see Orvieto, I suppose we can go a little further south.

Do you know if they'll charge extra to drop in a different city than where we pick up?

The Orvieto Hertz office is no longer (at least as of summer 2016) directly across the street from the train station. Walk a block down the street, cross through the gas station parking lot, and cross the next street. There it is. It is no longer visible from the train station, but still easily accessible by foot.

Orvieto has Hertz only.
Chiusi has Hertz, Avis-Budget, Europcar.
All are near the respective train stations.
There are no extra charges for dropping off at different locations within the country.
The choice is yours. I personally always drive all the way down to Rome and return it there. But to each his own.

Ah helpful, thank you.

My husband is doing the driving and very nervous about traffic in Rome. He's more comfortable driving in the country without as much congestion. Plus this way we could actually see Orvieto.

I just made another post, but will ask here - thoughts about where in the countryside to stay if we have one night between Siena and Rome? Montepulciano, Orvieto or elsewhere?