well if someone with the last name of Schafer is reading this, I'll say some intelligent and thoughtful things now.
Firstly, Invader Zim was cancelled because Viacom's stock went down, so they cut the show since MONEY IS SO GOD DAMN IMPORTANT WE MUST HAVE MORE YES YES YES.
On that note, if Double Fine were to be commissioned to make an Invader Zim platformer, that would be awesome. How to translate the three-dimensional impossibilities from the show would be another matter.
As for the original topic, the idea of a Psychonauts sequel seems appealing, but think about it: the game is so rich in history, depth, characters that it seems fertile for a sequel, yet on the other hand the game itself is a complete work of art, a masterpiece in itself, so to make a sequel that could top the original would be a nearly impossible task. But then again, this whole thread is hypothetical. I'd be content if there was no Psychonauts sequel, because Double Fine would have made another amazing, original game instead for us to adore.
As for the worlds:
Inside the mind of a person struggling with Obsessive Compulsive Disorder would be interesting. Endless panels counting from one to four, a creepy crawly contamination that scratches its way through the person's imagination, having him obsessively clean over and over even though the OCD keeps making new germs. You try and shut doors but they keep opening by themselves, stovetops burn even though the power is off, and you have to reach the depths of the contamination zone to fight the OCD monster, a giant gelatinous filthy beast that makes this mind hell.
I also thought what the mind of someone who eats to feel better inside is like. Probably some bizarre landscape where magma that screams with anger and sorrow is drowned by big chunks of food that fall from the sky.
Doctor Loboto's mind would be fun to see, it could be like an old black-and-white scifi film like Frankenstein, with the monster being Loboto's id run amok.