I don't have access to a full version of Painter, but my experience with Painter Essentials (2, 3 and 4) has been frustrating for anything but doodles. The paint program I like best is ArtRage (2 Deluxe). It's very simple, but the tools work the way the real tools work, and it has true layers with all the necessary way to combine them.

In spite of the fact that it wasn't designed to work with color, I'm mostly fine with using Manga Studio 3. Again, the tools have an amazingly intuitive feel, and there's no unnecessary complexity. (If I want complicated, I use Adobe Illustrator.)