I'll second the recommendation for Sirenuse. It's right in the middle of town, and the walk to the beach didn't bother us (we're not lie on the beach folks tho). Great service, very nice room--spent one evening sitting on the balcony listening to the choir from the church. Has a great sauna next to a plunge pool in the spa area. Restaurant was excellent.

Followed that with the St Regis Rome mentioned earlier in the thread. Enjoyed it greatly (especially the morning coffee via butler service), but I wouldn't consider it in the same league. Highly recommend it for Rome, since you'll mostly be out and about and the hotel is very nice (esp if you have SPG points/status).