It's kind of hard to offer any real advise if we don't know how much time you have for Italy.
I did a 14 day trip Italy last fall and spent 4 full days in Venice (side trips to the mountains, Vicenza and Padua), 4 full days in Florence (side trips to the Chianti region of Tuscany and Pisa/Lucca), and 3 full days in Rome. Although we had been to Venice and Florence before, I still wish we had spent more time in each. Rome will be a repeat of at least a week next time...
If you have the luxury of that kind of time (or more), I would recommend staying in apartments versus hotels. It makes life much comfortable. You can spread our a bit and have a sanctuary in which to relax between major sightseeing events.
In Italy, every church is packed with artwork. I think I read or heard somewhere that the Vatican City contains over 70,000 pieces of art - almost all historic in nature. So, it is very overwhelming.
Something else to remember, most museums in Italy are closed on Monday and a lot of the churches have reduced hours on Sunday (for worship services). Also, the big museums have reservation systems. So, you need to plan accordingly.