I've been a big fan of
Color It since I first installed it on my 68k Performa 475 in 1994. It's recently been updated to run in OS X. It's relatively cheap ($60), and really good. The main problem is that it's very clearly a port of an OS 9 program. It's got some quirks, it's got some bugs, and worst of all for new users, they don't offer a demo.

As an old user, I took a chance and bought it, and I'm glad I did. I tolerate its quirks, because it's just
so much better than everything else.
As much as I love Color It, your needs may be different from mine. So I recommend checking out some free (or cheap-with-demo) products first. If they suit you, great. If not, give Color It a look. Here are some apps that are good for what they do:
Graphic Converter. I think it's included on new Macs, so you should already have it installed.
Compositor
Pixen, which is geared towards 2D sprite design.
Seashore, a native OS X program based on the Gimp, but without most of its power.