The Binding of Isaac/Fridge

Fridge Brilliance

 * All of the Seven Deadly Sins mini-bosses have an unique sprite not seen in any other enemy in the game... All of them, except Sloth, which is just a lazy Palette Swap of the Globins! That's a subtle, yet incredibly clever and ingenious joke.
 * The familiar you get from obtaining the Cube of Meat can push your bombs around, which can often spell disaster for you. If you get three Cubes of Meat, he will get his own body and follow you around. However, he'll still push your bombs around. Getting the Fetus in a Jar item makes it so your only attack is bombs. It also gives you a top hat and a monocle, reminiscent of Dr. Fetus. Combining the resulting bomb-spam and Meat Boy will probably kill you, because Meat Boy will often push your own bombs back at you. Could this be Meat Boy trying to get revenge on Dr. Fetus?
 * Whore of Babylon transforms the character into a demon with high attack power, but only when you have only one heart - AKA when you are near death. ??? does not have regular hearts, ever, therefore maintaining WoB always active. Makes sense, since he is a Dead Blue Baby, and therefore as close to death as possible.
 * Look at the names of the playable characters: Isaac (a sacrifice to god), Judas (a traitor), Cain (a murderer), Magdelene (a whore) and Eve (the first sinner). Says a lot of what Mom thinks of her kids, doesn't it?
 * That says more about what Isaac thinks of himself, given that the other characters are Isaac in various costumes...

Fridge Horror

 * Mulligans will occasionally spawn in a room with fires in it, and almost inevitably they'll end up killing themselves by walking into it. They're too stupid to notice it's there, right? Then you remember that they're people who are being horrifically mutated into hives for insects, and it's clear from their sobs that they don't like it, and you realize that they're probably trying to commit suicide.
 * Same happens when they're left alone for a while, they'll just decide to blow themselves up.
 * The corpse that's in both the shop or hidden rooms has a uncanny resemblance to Greed. At first, seemingly a coincidence. Then the fact of Greed only attacks in these rooms implies that for whatever reason, Greed is playing dead on the occasions he doesn't attack...
 * Also Fridge Brilliance because his name is greed, and when he sells you things he...you know...takes your money.
 * When Isaac picks up the Steam Sale item, it shows Isaac with a sale tag on his ear. Has Mom been selling Isaac's body to pedophiles as a means of making money?
 * There is between floor nightmare were Isaac is suffocating in chest. Beating It Lives first time gives you ending where you find ??? in chest. ??? is dead. There are few endings that imply that Isaac went into chest. Do the math.