We had taken a 'guided tour for individuals', covering the Museums and the Basilica. I really enjoyed it, especially as they show you the important bits, rather than you get tired seeing the first bit and then when the best bit (Sistine Chapel) comes about you are exhausted!
You can find the tickets from here. Then select 'Buy tickets online and skip the queue' and then 'Guided tours for Individuals'. There was barely a queue when we were there (i.e. waiting for the person at the window to finish, but for some reason it was a very quiet day).
If you are interested something else we enjoyed was the Scavi tour.
What time of year are you going? It makes a big difference as to whether you need to book ahead.
We went this sort of time of year which I would recommend - weather was lovely (t-shirt weather, though it did rain once) and most of the tourists had gone (I think main 'season' ends around October). We therefore didn't have to book or queue for the Vatican (or anywhere else for that matter).
You can prebook an entry time. However it will still be congested in the Raphael rooms and Sistine chapel . Less so if you book a time very early and head straight there though. By 11am the coach and cruise parties arrive.
Once inside make your way straight upstairs as the lobby is busy as people buy tickets and groups gather and wait for those using the loos there. You will need to exchange your online voucher for individual tickets at the ticket office on the first floor.