Don't get me wrong, I still use Skitch1 for quick and dirty screenshots and annotations. In fact, I use it more than Layers. But Layers gets my vote for coolest screenshot app of all time.

Everything. On. Your. Screen. Is. A. Photoshop. Layer.

Do I need to say anything else? Try it yourself, they have a free trial.

Get Layers

1. 1. The observant among you will note that I wrote this review before I wrote about Skitch. Isn't retroactive continuity great?