The main destination of our Rome day was actually the Vatican City, the home to the Pope and the headquarters of the Roman Catholic Church. We did two tours of the Vatican in one afternoon (it was doable but we did feel a bit rushed) - Ufficio Scavi Tour and Vatican Museums & Sistine Chapel Tour. We really enjoyed the popular mainstream tour of the Vatican Museums & Sistine Chapel a bit more. If you have a strong interest in religion and/or archeology, we think the Scavi tour is a must-do. Otherwise there are just so many more art and architectural masterpieces to see in the Vatican Museums & Sistine Chapel. We were very impressed by the collections inside the Vatican Museums and wished we could have spent more time there.
Skip the queue and reserve your tickets online to the Vatican Museums & Sistine Chapel on the official site. They do charge €4 extra per ticket as a reservation fee (so you pay €20 online for a full-priced ticket vs. €16 if you buy in person) but you save a lot of time.