idk if 21 knows or plays video games that aren't major titles, but if he knows anything about Persona by osmosis (it's a big franchise), he probably knows or has heard of these things.

People being pushed into televisions
Levelling up through taking girls on dates
Adachi is a misogynist/the "bitches and whores" meme
Naoto is a crossdresser
People shooting themselves in the head and monsters coming out. Naoto would have no idea wtf because that's from game 3 and she's from game 4, but 3 and 4 blend together.
You can get Jesus and Satan as Pokemon Personas