I am planning a trip for the Fall and have the following rough outline:
London - 6 nights
Sienna - 4 nights
Amsterdam - 3 nights
uncommitted - 4 nights
I have been to Roma several times, so it's not mandatory for me to spend time there, though I would like to visit the Vatican if possible as a day trip.

I already have Florence on my schedule as (multiple?) day trip(s) from Sienna. I will add extra nights to my time in Sienna if other day trips are feasible.

Is a day trip from Sienna to Roma feasible? Any idea how much time would be spent in transit (via train)?

Is a day trip from Sienna to Todi feasible?

Any suggestions on other day trips from Sienna?

Rather than multiple trips back and forth to Florence, I'd spend at least one night in the city.

Will you have a car? What are your interests? Wine, food, architecture, shopping, art, scenery?

You can check train schedules at:

http://www.trenitalia.com/en/index.html

Siena to Todi by train would be a minimum of 4 hours each way.

Siena to Rome by train would be 3 hours each way.

Florence is a too rich city to visit going raound and round without any help. I suggest you taking advantage of some exeperienced local guide as http://www.guidesinflorence.it cause you spend some money but you earn time and beautiful sightseeing...

Hi K,

I suggest 2 nights in Florence and 2 in SIENA.

You can take the train from Florence to Rome TE
www.trenitalia.com/en/index.htm
or the bus (recommended)from Siena to Rome Tiburtina for 5E. http://www.senabus.it/

>...uncommitted - 4 nights

If it's Sept to mid-Oct, why not the Amalfi Coast before going to Amsterdam?

I second Ira here...at least with one night in Siena. I've never stayed in Siena...only been there during the day. But I saw enough to know that it would be a drastically different, and better, city after all of the day trippers departed. Florence can be your base for a few days if you really want to get outside of that city, but I'd find plenty to do there in two or three days.