I was at a comedy club in Knoxville a year or two ago (I never can remember what it's called, but it's near Cotton Eyed Joe's and is rather famous) and Donald Glover was opening for Brad Williams around the South.
And he started this bit that starts with "Did you guys know that Dolphins rape in the wild? Humans aren't the only animals who do that."
I was fairly inebriated at that point, 2 for 1 drink night and I wasn't driving, and I knew this fact. I was also sitting near the front. So I just naturally started nodding my knowledge of knowing while eating and looked up. He saw me nodding and goes "This guy is shaking his head yes waaay to much. He knows from personal experience, get some therapy with the settlement you should've gotten from the aquarium man."
The place died, but I probably laughed harder than anyone else there. To me being able to improvise, involve the crowd, change your set and your rhythm at all is an impressive thing for a comic to do. Bonus points if you can make fun of someone.