When you fly from the States, take a late flight that arrives into Rome Fiumicino early in the morning. If you've done yourself a favor you caught a few winks on the flight, when you get there you have at least 4-5 hours to get busy, before the jet-lag reminds that it is time for a nap:) Take a chance to book the Mecente Palace Hotel on Via Carlo Albert! What a stunner it is, and the rates are very competitive. The best feature of the hotel is the rooftop reserved for guests. The views over the Santa Maria Maggiore and on toward the Vatican are worth every dime. Cocktails and food up there too!
Seeing Rome is a monumental task. The city checks off so many iconic landmarks that you have to make a great itinerary and stick to it. Of course, being flexible is important too- the piazzas are chock full of bars, bistros and places to sip Chianti. This is where you may fall off track
I've been to Rome twice and made different choices of itinerary each time. I feel I will need several trips back to feel like I've made progress. BUT do not miss the Vatican including the Sistine Chapel and St. Peter's Basillica, the Trevi Fountain, the Pantheon. Eat pizza, some tapas and gelato. And savor all those amazing Italian wines!
PS If you'd like some feedback about your own itinerary feel free to contact me. I am happy to help with some guidance!