Since I'm not a religious person, my interest in the Vatican primarily stems from my high school obsession with Angels & Demons. That, and everything about it is sort of shrouded in mystery and scandal. I'm sure at some point I learned some things about it in AP European History but that knowledge is long gone. Luckily I had a great tour guide to explain what I was looking at in the museum and church.
I don't usually enjoy guided tours because the explanations provided tend to exceed my attention span, but Valerie (of Rome Walks) was awesome. She paid each person in our intimate five strong group careful attention, answering all our questions and catering to our specific interests. Valerie was both highly knowledgable and engaging - less like a historian and more like a storyteller.
She spoke at length about Michelangelo and Raphael (the artists behind the Vatican's most famous paintings) and their differences in style and personality, as well the scandal and drama stirred up under various popes - like the Borgia pope who allegedly organized orgies and Julius II who was the driving force behind the city's most ambitious building projects.
After going through the museum, we took time to admire the Sistine Chapel before ending the tour with the famous St. Peter's Basilica. No words can describe the beauty, grandeur and intricacy of it. Not even the photos do it justice.
Note: Tour groups get to skip the line to get inside. Queuing outside for hours to get in might not be such a big deal in cooler months, but in 90 degree weather it's probably the last thing anyone really wants to do. And unless you're already a Catholic history nerd, you'll probably learn something new.