My wife and I just recently started watching a new TV show. She has a weakness for crime dramas with a touch of fun - she loves Castle, for example. And Numbers. And Bones. We both loved Monk. And now we're watching Perception.
All of these shows have main characters who work as consultants to the regular police department (or FBI). The most of the viewpoint characters are damaged in some way, which makes them more entertaining and interesting. The viewpoint character in Monk suffers from obsessive-compulsive disorder. In Perception, the character has schizophrenia, and often sees characters who aren't there.
The difference between the two is that, in Monk, we can't see the OCD's effects directly. We can see, indirectly, what Adrian Monk is forced to do, but that's not the same. In Perception, we can see the imaginary characters (and other things) that Dr. Pierce interacts with. It casts doubt on the existence of every single character on the show other than the lead. In fact, I occasionally find myself wondering if the entire show isn't in the lead character's mind.
Last night, I was playing our bi-weekly Dresden Files game. During the game, I realized a few things about my character's headspace - and that's always a scary thing. Doubly so in the Dresden universe. After the game, we were hanging out and chatting, and one of the other players said something to me (and the rest of the group) about her character's perspective. What if Harry Dresden is an unreliable narrator? What if he really is the villain of the piece who is spinning a story for us? What if the White Council was right to not trust him? That's the perspective her character brings to the game. And it's not entirely outlandish, even using Butcher's writings as your source.
So how much of this can you fold into your game? A lot.
Have a player who takes schizophrenia as a flaw on a regular basis? Ask one of the other players (in secret) if he wants to play a hallucination. Tell him to be careful not to directly interact with the rest of the party. It's entirely possible that the rest of the party will try to interact with him - he'll need to learn to shrug it off. If the party decides to follow the hallucination's lead at some point, then clearly the schizophrenic character repeated what was said.
The imaginary PC also had to be prepared for a lot of hitting but not doing damage. Or having the foe just shrug it off. It also means that PC shouldn't take a roll essential for the rest of the party.
Want to mess with your players in a superhero game? Do to them what JJJ has been trying to do to Spider-Man for years - turn public perception against them. Maybe that last villain they busted had been waging a PR campaign against them. Or maybe it was a matter of one press reporter was in the wrong place at the wrong time and so it looks like the PC's did something.
Or maybe they are villains and didn't realize it.
Batman's cave is filled with trophies - what if those trophies are pieces to a doomsday machine he is building? What if his Rogues Gallery keeps busting out of Arkham with his help? He has manipulated his villains into doing his bidding for years. If the Mad Hatter's latest theft - a microtransmitter - isn't recovered when the Hatter is caught, who would notice? There is, after all, a whole warehouse full of components for whatever the Hatter was building.
In games which have a merit/flaw or advantage/disadvantage system, I very rarely see a character without one of the drawbacks. After all, they are free points, right?
As a GM, the players rely on you for every single scrap of information about the world around them. YOU control their senses. All of them. Want them to hallucinate a smell of flowers that isn't there? Tell them that they smell flowers. Want them to notice a detail somewhere? Point it out to them.
Just remember that you don't necessarily need to be a reliable narrator.