Pyxel Edit is a pixel art drawing application especially designed for working with tiles. Place tiles to form a level, edit them directly to see how they all work together, then export your tileset and the level data, and load it into your game. Tiles can even be flipped and rotated, still being editable and synced. This feature is inspired by the awesome Pixothello and Cosmigo Pro Motion, but taken one step further.
It also supports making animations, and exporting them as sprite sheets or animated GIFs.
Pyxel Edit is built in Adobe Air and runs on Mac and Windows. (it reportedly also runs well in Linux under Wine)