Before You Go
There are a few things you'll need to plan ahead of time to set yourself up for a successful trip. Purchase museum and attraction tickets before you travel (or at least a few days before you plan to visit), because popular tourist spots book up fast. Without a ticket, you could be standing in an hours-long line just to get in.
As far as getting there, we flew into Venice and out of Rome; this is your best option so that you don't waste time backtracking to your original destination to catch a plane home. You could start in Rome and end in Venice, but the quiet (read: no cars), laid-back atmosphere of Venice made it easier to get acclimated. To make this work, you'll want to choose a flight that puts you into Italy early in the morning so you can sleep on the plane and hit the ground running when you arrive. If you have the extra time in your schedule, though, fly in the night before and get a good night's sleep in a real bed before your sightseeing begins.
Another expert tip: Cell-phone service can be spotty, and Google Maps may not always be able to save you. Pick up a detailed paper map in each city so you can easily navigate by foot or on public transportation. Use the more reliable hotel WiFi to pinpoint the exact location of any restaurants you are dying to visit, and mark them on the map before you head back out.