Make sure you Google map potential hotels and then get the time to walk to the center/various places. That will at least allow you to screen out places that are far from downtown.

Being in the correct location in Florence does make it easier to slip into its rhythm. Even the two Westin properties on Piazza Ognissanti, which is not far from downtown, presents a little too much overhead in getting to downtown. Personally, I like staying Oltrarno. It's an easy & charming walk to the Uffizi across the Ponte Vecchio and I find the neighborhood very comfortable. We'll be there in early November.