But really, I don't know that any modern system could possibly reproduce the experience of Mario Paint. It was all about the limitations - the tiny color palette, the single octave, the crappy tools, the meager nine animation frames - the point of Mario Paint for me was always the challenge of figuring out how to do things that the program really wasn't designed for you to do.
However: I bet that they could make a pretty fantastic update on the fly-swatting game for the Wii!