I don't remember any of the many houserules I used back in the 2e days. They probably weren't that great anyway.
In 3e, I kept things pretty simple. Aside from stylistic houserules
based on the setting, I did make one deliberate change to the Toughness feat. I had the feat also add -3 hit points, in addition to the +3 hit points that it normally added (meaning a character who had taken the feat once would die at -13 hit points, instead of -10). This made the feat particularly attractive to someone who also had Diehard.
In 4e (and other games I currently run, such as an E6 Trailblazer game), aside from stylistic houserules
based on the setting, I utilize a variety of rules that provide incentive for the players to play the game I want to run. In particular, two have been extremely beneficial to my games:
1 - Karma Points: The idea is not new, but in my games, I allow for both heroic deeds accomplished within the game
and deeds done by players outside of the game
that specifically make my job as DM easier to accumulate such points. These points can be used in
any game I run for a mechanical benefit (turning a hit into a miss or vise versa, turning a hit into a crit, making a save, etc.), or, more popularly, to change the plot on me. This type of usage has significantly altered the course of campaigns.
2 - Levels Through Quests: The problem with XP is not that it's overly-fiddly (although it is), it is that it assumes that the players fight (and succeed). A lot. Some will (and that's okay with me), but some groups will (and do) prefer to find other means of accomplishing their goals, and I want to reward that behavior no less than I would a hack-and-slash party. I do that by advancing players a level based on a number of quests accomplished (with each minor quest being equal to a fraction of a major quest--2:1 or 3:1 work pretty well). This puts the focus squarely on getting the job done, and does not care what means the party chooses to do it.