1) The architecture looks like what you end up shooting in a lot of in places (rotundas, columns, fountains, etc).
2) The scale is huge, so you're forced to work with some difficult perspectives and composition choices.
3) There are tourists everywhere, constantly walking into your frame, giving you little time to think about the shot you're composing.
4) The light is a bitch. UV and haze everywhere. Washed-out sky against faded stone, with an eight to ten f-stop jump between the shadows.
5) It's been shot a gazillion times, so finding a fresh look is a challenge.
I'm going to start making it a habit to go here more often - especially when I get a new camera or when I'm planning on travelling. It's a great place to practice.