If you're booking reward flights, you can book them as singles. I've only ever booked reward flights ex UK so I have no idea about what the rates are for flights ex the USA but with BA, I'm thinking that (for coach rewards) you'll need to transit LHR so you may be looking at bigger mileages to get out of London and on to Italy. Can you get any value for your miles on AA?
Regarding the reward stays, Hilton Molino Stucky in Venice is great but rewards are hard to come by there. In Rome, dont be tempted to use the Hilton at the airport, its unremarkable and very noisy
Did you consider trains between any of the points? Could be an experience...