12 years ago (low season too)-- so grain of salt:
St. Regis in Rome. Very nice hotel. Huge room, but seemed a bit far from major attractions.
St. Regis Florence. Stayed when it was still the Grand Hotel. Loved it. Had a fresco on the wall and view of the Arno. Location was also great.
Gritti Palace: After a general strike forced us off the train and in to rental car from Florence to Venice, the Grand Hotel called the Gritti Palace to let them know about the issue. Gritti Palace couldn't modify our reservation, but they upgraded us to a great room directly overlooking the Grand Canal. Venice is small, and so everything was convenient to the hotel. A great experience.