Obviously, if you keep your toothpicks in uber cute tooth pick holders than this task is made so much more pleasant. Like my little piggy that i found in NYC. I brought him home with me, and now he lives with my baking stuff. I kind of want to eat him. (Don't tell him though.)
I start stalking all my cupcakes around minute 15 and when they look good i stick a toothpick in the center of the cupcake. If the tooth pick comes out clean than i take them out. If the toothpick has batter in it, than i leave them be.
This is what a "clean" toothpick looks like. A few cupcake crumbs, but no wet batter to dirty the wood.