My favorite 20 Questions experience was when my friend Dave was answering. He had picked some sort of video game protagonist. We almost had it, with one question left and then a final guess. We narrowed it down to most likely either Duke Nukem or Mario (I don’t remember how…), although we weren’t positive we hadn’t missed some obscure character.
So, the question we decided to ask to choose between the two was “If you replaced the character with a flesh-eating alien, would it affect the plot?” Our reasoning was that Mario was a plumber in love with a human princess with a human brother, whereas Duke Nukem was just a device to shoot aliens. We got it right — it was Duke Nukem. Although the question is admittedly vague enough to warrant argument over exactly how crucial someone is to a plot, we all got a kick out of it.
A runner up favorite is “If you poke it, will your finger then have liquid on it?”