Chrome/Firefox/Safari: Want proof that HTML5 is the way of the future? Try Sketchpad, a surprisingly robust online painting app that doesn't require Flash, Shockwave or any other plug-in — just a modern browser and a mouse.
Sketchpad also offers a handful of control windows you can move around and keep open. If the app supported drag-and-drop file imports, as Firefox 3.6 does, this would be a truly robust, and almost desktop-replacing, web app.
When you're done with your efforts, hit the save icon and your image pops up in a new tab, ready to be saved. Sketchpad is free to use and works on any browser that supports HTML5 — including, it's been suggested, in some mobile devices, though we had very little luck actually painting with an iPod touch and Android device.