House Rule for my undersea campaign: "Human PCs are allowed... for as long as they can hold their breath. Thereafter, they are required to take one of two prestige classes; Anchor or Bait."
No matter what game I'm running, if someone says "Hastur" at the table, I roll to see if he shows up. Could be CoC, D&D, M&M, V&V, Toon, whatever, I'm rolling it.
In my 3.5 campaign, the Ranger's player convinced me that in addition to Spot and Listen checks, as a Ranger, he should get a Smell check. If he rolled badly, what usually happened was that what the other party members (those that made the check, anyway) would See or Hear whatever it was from a certain distance, whereas the Ranger had to be right up close to Smell it. Usually withing striking distance.
Had a DM rule that since lead blocks divinations, lead must be undetectable by mineral detection. As a result, lead became as valuable as gold in his world.
Also had a player spoonerise Horn of Fog to Forn of Hog, and it was decided that this was what the item was called in-world thereafter.
Played under a DM one campaign who had a houserule that if anyone was late from the game they had their characters gender changed. Second session into the campaign there was a public transit strike and the entire game world was struck by a mysterious genderflip.
Then there was the DM who had huge difficulties with the grapple rules, and had the Mortal Kombat theme playing every time that he pondered them over. If he couldn't figure out what happened by the time the song ended he just flipped a coin.
Was in a Conan game where if a fight didn't take place by the end of a session one would spontaneously erupt no matter what the situation. Felt appropriate for the game.
Was also in a campaign where all dragons meowed. This stemmed from an incident on the first day where a player forgot exactly what his familiar was, thinking it was a cat when the dm had agreed to give him a pseudo dragon.
I played a Wild Mage from the 2nd Ed. Tome of Magic the GM to let me roll for a wild surge instead of a 1st level spell if I wanted to. So much wonderful d100 randomness occurred!
Not so much a house rule as a gift from the gods....
If you bring an offering of sacrifice to the DM/G.O.D. (Game Operations Designer) a wondrous thing will happen in direct correlation to the awesomeness of the offering. (And it's not a bribe, bribes are bad.. )
I.e.
DM - (roll, roll, roll) Your character has sustained a fatal wound and has began to bled to death.
Player - Hey look a bag of Oreos!
DM - I mean the monster's attack has rebounded off of your armor and the monster sustains a fatal wound.... (pockets the bag of Oreos for later consumption)