The highlight of visiting Rome was the "Holy See," otherwise known as the Vatican. I would also recommend the Coliseum, the ever impressive "David" by Michelangelo, and of course shopping.
Quick Tips: Rome is best on its' off seasons. During the summer it’s hot, crowded, over-booked, and the Vatican only allows you a couple of minutes with the Sistine Chapel, which is a crime. Many things are closed down during August, which is when Europe traditionally has vacation.
Best Way To Get Around: Rome has all the usual European transportation including: the subway, buses and taxis. I recommend a personal taxi driver. Read my thoughts on transportation for more information.