Vatican Museum

I agree to go in the afternoon; there was hardly a line when I went. This museum is well worth its entrance fee. There is so much to see.
I would recommend spending some time in the exhibits before the Sistine chapel. I saw many people walking through the exhibits without looking at the pieces just following the signs to the chapel, but all of the pieces are beautiful. Once you are in the Sistine chapel you probably wont get a chance to go back to some of the other exhibits because there is a general flow in the opposite direction, and the museum is somewhat maze-like.
The Egyptian collection was great as well as the courtyard, which houses Laocoon and his sons (as Eric mentioned.)
The audio guide was also a great help. It’s only 4 Euro per person and it highlights some of the more important pieces to explain.
The halls and rooms that hold the pieces are great. Most have decorated ceilings or frescoed walls. The museum does a great job of matching the designs with the items. While other exhibitions I saw in the Castel Sant Angelo clashed between the Roman fourth style wall paintings and modern art, the Vatican combined them so that you don’t lose focus. The Hall of miscellaneous sculpture did this particularly well.
If you go with a tour group make sure the tour in the museums is more than an hour! We decided against the tour group when we learned this, there is too much and it is well worth it to spend double or triple the time.

The Vatican Museum was outstanding, and not only for the sistine chapel! It was abit of a nightmare to find because you have to walk from st peter's church and its right round the corner along a very long windey brick wall but it was well worth the hunt! I spent 4 hours in the whole museum the exhibitions especilally the ethnological one and egyptian one were really interesting! The ceiling fresco are all in perfect condition so make sure the camera's charged. All i would say is avoid doing it as a tour group i did it alone and you get to listern in on tours as you go round but you can go at your own pace, i went peak season and the tour groups everywhere became a tad iritating! They say no camera's also in the sistine chapel but to get round this turn off your flash and hold it still at waist height and do it on the sly because trust me you will want to get some memories of it!

I agree with Eric, the Museum is incredible. I just have two tips from my visit there:

1. Go in the afternoon if at all possible. The lines will be long no matter what, but in the afternoon they are FAR shorter than first thing in the morning with all the toursists who want to check it off thier lists.

2. The sheer number of people can be overwhleming in the Sistine chapel, and Eric's right about the 'silencio' guy (or the British woman who tells English-speakers to kindly be quiet and not take photos). I'm a painter so I knew I had to really spend some time with the ceiling. I just found a piece of bench, tried to block out everything around me and looked up for a good 20 minutes. Chances are this might be the only time you'll see it in real life, and unlike some other famous works of art, it really does live up to its hype, so it's worth spending time with.

In short, this is one of the most amazing collections of art in the world. Even with all of the other amazing attractions in Rome, this should be at the top of your list for things to see. Instead of trying to hopelessly summarize the entire museum, I'm just going to focus on my favorite part: the inner courtyard.

This small courtyard contains many ancient statues of staggering quality. Each work is situated in a small, outdoor alcove and there is a real sense of discovery and wonder as you walk around the courtyard, wondering what great work the next niche holds. My favorite statue here is Laocoon and his Sons. During the Trojan war, Laocoon was a priest of Troy who warned its inhabitants about accepting the now infamous Trojan Horse. After his warning, two giant snakes sent by the gods (probably Athena) emerge from the sea and basically strangle Laocoon and his sons. The story is grisly, but the statue is spectacular!

The discovery of these ancient statues also played an important role the flowering of the Renaissance. Laocoon, carved by three brothers in Greece over two-thousand years ago, was hailed by the Greeks as the most beautiful statue of its time. When it was unearthed 1500 years later in Italy, the artists of the Renaissance were motivated to create even more beautiful works of art, and in a sense were competing with antiquity. Also, since ancient Greek sculptures were all the rage during the time, many artists (including the great Michelangelo) tried to create works and pass them off as ancient Greek originals.

This is just one small, small part of the museum and I haven't even mentioned the Raphael rooms, Michelangelo's Last Judgement, or the Sistine Chapel. It's all worth it (although the guy shouting "silencio" every 3 seconds in the Sistine Chapel can get kind of annoying...). Bottom line: go here.