I stumbled across a neat little program last week called FireAlpaca that's a nice, lightweight drawing tool. It's a hell of a lot faster than Photoshop is at drawing, and its save-files are roughly half the size of Photoshop's PSD. It offers the ability to save as various formats, including importing/exporting PSDs, which is pretty convenient.

It's by no means a photoshop alternative, and it doesn't appear to support CMYK yet, but it's a lightweight drawing tool that's small and fast. It doesn't have much in the way of preferences for the application or the tools (which is a refreshing difference from Photoshop with its nested preferences, modular dialogues, etc). All the tool preferences are in modal palettes, and they're attached to the expected Photoshop keybindings (b for brush, g for bucket, etc) and seems to work perfectly with a tablet as long as you have the drivers installed (I've got an Intuos).

FireAlpaca is built with QT, so there appear to be stand-alone binaries for both Windows and OSX (but oddly not for Linux). I know there are tools like Paint Tool Sai, but I've not used those since I don't use Windows, so I welcome an alternative to Photoshop (which is good for painting, but very heavy) and Manga Studio (which is good for comics but not painting).

Example of the interface: http://i.imgur.com/xxKRB.png

While it doesn't strictly adhere to OSX interface convention being built with QT, it is clean, fast, and functional.

So yeah! Check it out. It doesn't appear to be FOSS/GPL software, but it is free and does use a few FOSS components.