Lemme put in a vote for Florence.....its an all-walkable place, so no transit concerns as in Rome....if you like to see major art in the palaces and buildings the art was designed for, then Florence is the place......High speed train from Rome to Florence (90min) is easy (and low cost with advanced tiks from website), and plenty of hotels in walking distance from Florence train station.
High-speed trains continue from Florence to Venice (2 hrs), so we did Venice as a day trip from Florence....enjoy!