I haven't read the other replies.

If you are going during any part of the busy season, buy your Vatican tickets before going, preferably for first thing one morning. It gets super crowded in some of the rooms as the day wears on.
For the Colossieum, I suggest the Roma Pass. You can go to a less crowded place first, like Palantine Hill, and buy it there, I believe. I think you can also buy it at a TI?

Personally, I would not book a guide for either-- we much preferred to read the Rick Steves guidebook beforehand and explore at our own pace, but that's really based on personal preference. Have fun!

I really like Context Tours. For both of these locales you will not know what you are seeing and will not be able to appreciate them without some additional help. I say that as someone who usually doesn't use guides. Without, you are mostly going "Wow, what a cool building."