Hands down, the most fun I've had doing pixel art. Extremely useful and comprehensive features, with regular updates. The interface itself is pixel art, so what better environment to use when making your own pixel art?
Super simple and powerful tile map editor. If you have 2D Toolkit for Unity, you can import these tile maps directly into Unity. So cool. (Even if you don't have 2D Toolkit, you can import the maps, but with 2D Toolkit it's literally the click of a button and you're done.)