By "best" do you mean the fastest? From Rome, you can reach Siena by car, bus or train, they all roughly take from 2 hours and 40 minutes to 3 and a half hours (slowest is by train).
By car, you could take this route by while bus you would need to go to the
Bus Station Tiburtina (outside the train station Tiburtina) and take a SENA bus. Check bus timetables here. Bus takes roughly 2.45-3 hours.
By train, you would need to change trains in Chiusi which is why the trip takes longer - there is the time in between trains to wait out. The trip takes from 3.5-4 hours. You can check timetables on the Trenitalia website.
So the fastest would be by car - but the easiest in the end, if you don't want to drive, would depend on where you are in Rome. If you are close to the main train station, Termini, I'd take the train rather than the bus since I'd have to figure out how to get to the other train station first. Traveling by train is really easy and comfortable and the time passes quickly - bring a good book or enjoy viewing the countryside as you travel