Transmetropolitan/WMG

Transmetropolitan

Think about it. They may be practically immortal, have the ability to assemble just about anything out of literally thin air, and likely possess quite a few other incredible abilities. However they're not omniscient, don't seem to have any ability to reproduce themselves, and it is implied that they are unable to leave the City. Most important is that "going foglet" is a one-way process, which would also imply that once you go foglet, you can't change into anything else or make any modifications to the foglet form. It also adds rationale to the existence of the Farsight Reservation, which tries to do things more differently specifically because foglets are dead-ends.

Telling the "Revivals" the length of time that they've been frozen causes them to Go Mad from the Revelation not because it's so long, but because the world has changed so much in at most a few decades.
- Hm... I always thought it was being dumped out into the streets and seeing all the changes that triggers the first shock, and that the rest comes from failing to adjust to society after a lifetime back in their own.

It's just that they were so disgusted with humanity they left the known universe.

This probably falls into Reasonably Probable Conjecture rather Wild Mass Guessing, but I thought I'd throw out the idea and see what people have to say.
- ...That it was pretty explicitly stated the I-pollen was messing him up?
  - Nuh-uh, because ONE PERCENT HAHAHAHA.
  - Spider is a pretty messed up individual even before his two exposures to the I-Pollen, which were both present in the series, so I don't think that you could say that I-Pollen was entirely responsible for his attitude. It doesn't seem to be a matter of drugs either, although Spider's so rarely seen without them that it's hard to say whether he's just naturally like that.

It explains the Gladiator Wall, how uninhibited everyone is, the apocalyptic past Spider refers to, and how we got such exact mastery of the human genome.