What is the best way to travel from Siena to Rome?
Ann, My preference on that route would be travel by train. You'll need to take a Taxi from your Hotel to the rail station, which is at the bottom of the hill. Travel time is about 3H:25M, and there's usually one change in either Florence or Chiusi. Those trains changing in Chiusi are likely to be Regionale trains (DON'T forget to validate!), which don't usually require reservations. Those changing in Florence will use the Frecce trains from there to Rome, which will require a reservation. Happy travels!
There is also the SENA bus from the Siena city wall to the Rome-Tiburtina train station (www.sena.it). Travel time is about the same. Cost for the bus is less than the train.
I've been contemplating this same question today. Seems like the train is pretty spendy since they don't seem to offer any mini fares on this route. The bus is looking like a very viable option for 23 euros, and takes about the same amount of time.
regional train to Chiusi then an IC train to Roma Termini for 24.10 and 3:19
On Trenitalia, if you put in Siena and Roma, most train runs on the Trenitalia website will route you to Florence where you would transfer to a high-speed. Very few will route you to Chiusi. The fare with the high-speed can be 7.10E for the train to Florence and 45E for the high-speed to Rome. However, you can lock in a mini-fare as low as 29E on the high-speed if you book early. As mentioned above, the bus is less expensive and the travel time is about the same.