so here's my theory about this show
eric andre is trapped in this torturous state of limbo where he is forced to host a *beep* late night talk show.
this is why he begins each episode by destroying the set.
he's fighting against it with all he has but once he gives up, the set rebuilds and he's forced to host the show once again.
i believe the second season finale was proof of this. it was like he was using every fiber of his being to fight against it but in the end he ran out of energy and the show one.
in regards to the other people on the show:
i feel like they're remnants of what eric can remember of the real world. The guests are random celebreties who he either remembers clearly or doesnt (which would explain guests like Reese Witherspoon, George Clooney, Beyonce & Jay-Z, etc)
the pranks would be a reflection of eric's feelings of rejection from society that he felt in his old life. There's a lot that alludes to his sense of unworthiness within himself but the best example of this would be The Hannibal Buress Show episode where he is pushed to the background and Hannibal proves far more successful a host than Eric. Throughout each episode Hannibal is portrayed as the memory of an old friend used by Eric's mind to project his lack of self worth
Of course this is all just conjecture but its fun to theorize about shows like this one where so many questions are raised and none of them answered.