Pixelmator (Mac OS X). While it's paid software (US$30), it is an excellent program for those who are overwhelmed by Photoshop's price, learning curve, and (especially on Mac) lack of platform optimization. For me, it does almost everything I need it to do.
For Windows, I recommend Paint.NET along with a couple of plugins you can get on its forums. Very potent, free, and versatile.
Any platform: Gimp (raster - eg. Photoshop), Inkscape (vector - eg. Illustrator), and Synfig (animation - eg. Flash Pro). They don't work nearly as well on OS X, though.
That being said I prefer drawing and colouring by hand, and use digital editing for post-processing and Photoshopping.