Is it possible to make reservations for particular sites such as the Vatican Museum and other mass visited places in advance via the internet? Any suggestions to pass up the ticket booths and lines? We will be visiting in early October.

Yes it is possible at many sites. However the whole world appears to be at the Vatican Museum when it opens each morning. the best time to go is in the afternoon say from 2:30p on the tour groups are gone and it is much easier to see things. On the other hand the Sistine will still always have tons of people in it, to see it as it should be, you need to be there first thing in am, enter the museum, race to the chapel view and enjoy it, then back track and do the other museum stuff. JMHO

For the Vatican, you can book entrance tickets only or guided tours directly with them about two months in advance.
Tour info:
http://mv.vatican.va/3_EN/pages/z-In...zi_Visite.html

Reservations:
http://mv.vatican.va/3_EN/pages/MV_Home.html

For other sites, the 25€ 3 day (consecutive) Roma Pass might be beneficial depending on what you plan to see and how many days you will be there. You get free admission to your first two sites, discounts after that and a 3 day travel pass. Best value use of the pass is for the Colosseum/Forum/Palantine (counts as one entrance) and either the Capitoline or Borghese as they are the most expensive sites. The Borghese is timed reservation only (even with a pass) and you have to call to make the reservation.
http://www.romapass.it/p.aspx?l=en&tid=2

If you want to see the newly opened colliseum underground, you will need to book ahead -- preferably several weeks ahead. We didn't and were disappointed to miss it.

Thank you for posting this information. So confusing isn't it?

Another tip: If you are going to be there 3 days, get a RomaPass at one of the sites around the Forum -- either the Capitoline Musem or Palatine Hill, which have shorter lines. It gives you free access to several places (Colosseum, Palatine and Forum count as one) so you can avoid the ticket lines. at the Colosseum, keep in the line on your left at the entrance. I suspect the underground there requires advance reservations for the time of your visit, though.

fyi---The Underground tour of the Colliseum is not booking any dates after 09-30. It looks like there is renovation scheduled after that so it is unlikely the underground will be opened. I've been checking weekly for a month or so and recently read that major renovation has been funded by a private company.