Before we had Illustrator, before we had The Gimp....we had Mario!
Basically set up like any stock Paint program, this was the first title I knew of that made use of the mouse. There's a large selection of colors, textures and stamps, and even about 8 ways of erasing your drawing...almost as much fun as drawing something to begin with! There's also a small selection of "coloring book" pages, which is great for any younger kids who can only get the Fill tool down.
Creative types can have a blast with the animator, which let you do simple ones with up to nine frames (though the higher the frame rate, the smaller your image needs to be). Those low on the skills could use the selections of stamps to make moving Yoshis, Bowsers and other assorted Mario critters. Even better, you can set up a "track" to make them move across a background you design yourself.
Or perhaps you're musically inclined? Try out the composing feature. You can set it up for 3/4 time or 4/4, and instead of musical notes you use icons such as mushrooms, flowers, stars, and even animals to create different sound effects (try setting up "Twinkle, Twinkle Little Star using nothing but meowing cats, oinking pigs and mooing cows :D). There's a good selection of instrument sounds too, so it's all about how far your ability takes you.
The little mini-game (designed to help people get used to the mouse) is amusing - play as a hand with a flyswatter that's trying to squash some pesky flying bugs. Of course, some of them bite or sting (not to mention explode). Also worth noting - on the initial load screen, try clicking on each letter, and see what happens!
In this age, when almost everybody has Photoshop or its equivalent on their desktop, MarioPaint may seem dumbed-down. But it has a lot to offer to anyone who just like to piddle around with drawing and exploring their creativity.