Michael-need to know a few things to help you out....what do you like (hiking,museums,music)? You mentioned a guided tour-are you elderly or need the info in another language? A weekend doesn't do this city justice.Let me give it a try.Don't waste your time on a line when you can get tickets on line before you leave-I am of course talking about the Vatican.There is a dress code here....
The architecture is great-walk on your own and visit the Forum. If it is hot...head out for a tour of the catacumbs.Great way to cool off. Some beautiful plazas for late at night.Try to go at least one block away in any direction and the food improves 100%. The restaurants around the main attractions cater to large number of tourists and are design to pack them in and out. If you only have time to see one fountain-head out to Trevi.Read ahead and you will be able to have a better idea to what appeals to you. Have Fun

Context Rome has a great offering of tours in and around Rome. You might check them out.

There is also a "Free Walking Tour" of Rome that gathers near the base of the Spanish Steps in the late afternoon. We did it earlier this month and really enjoyed the guide's enthusiasm and knowledge. A tip at the end of the trip was suggested. Surely one of the posters with a better memory than mine can give you the right time.

If you buy a Roma Pass, you can bypass the long lines at the Colosseum. That would be my #1. Vatican Museums, including Sistine Chapel and St. Peter's #2. For such a short visit, I highly recommend private tour(s) of Palatine Hill/Forum on same day you do Colosseum. Search this site for Master List of guides. I highly recommend Francesca Caruso. Also can recommend Context Rome. Check out their website. You will love Rome!

Hey Michael,
if you're interested in guided tours, you could check out Baja Bikes. I did a bike tour with them in Barcelona and it was great! As far as I know they also offer bike tours in Rome. It's a good way to get a first impression and orientation.. Otherwise get a good guidebook and explore the city on your own...
Have a great time in Rome! Annie