For blender users, there is an edge finder called freestyle that does some interesting kind of hand drawn looks. This is something I had on my hard drive I did a while back that I did with it:
You have to download the entire blender program to try it out or else recompile it yourself. Keep in mind I just played around with it for a little while and it's a very large image. A smaller one would look better I think. Also, there are lots of other scripts for different effects.
Lots of interesting information on their blog that outlines how they do certain things. I quite like the idea of using perlin noise to draw more turbulent outlines. The algorithm is based off silhouette edge detection though, so runtime performance will take a bit of a hit over using raster based algorithms like sobel. Still, it might be interesting to bake the results to a texture and use that in real-time instead of doing any calculations, leaving the GPU to only process cel shaded lighting. While the author has been trying to integrate this into core blender since 2007, hopefully he can pull some strings because I've been doing some cel shaded work and this would come in handy for prerendered graphics.
Yeah, I was thinking more for 2d sprites. It's a long ways from real time because there's a pretty long wait on my old computer, but there might be some way to speed it up for real time. That would be interesting. I'd like to try a little 2d html5 game and it would be great for that.