You meet all kinds of comical teachers in Shin Megami Tensei: Persona 4, but Mr. Hosoi is the most memorable. He lectures players on Japanese literature with a hand puppet sort of like early Mr. Garrison. I can't say for sure if Mr. Hosoi was directly inspired by the South Park character, but the localization team at Atlus USA gave another nod to South Park by having Mr. Hosoi say Mr. Mackey's catch phrase "mmmkay". I don't remember South Park ever being a hit Japan so Mr. Hosoi an unusual and interesting addition for Persona 4 considering the game was developed in Japan.
Images courtesy of Atlus.