A lot of my house rules are setting-specific things, like alternate spellcasting classes to represent different traditions, and revisions of a few of the races. But I do have some generic house rules that I would probably suggest regardless of setting.
Hit Points and Wound Points
Hit Points heal at a rate of 1 per level per hour. In addition to your hit points (HP), you have Wound Points (WP) equal to your Constitution, or 3/4 your Con for small races. If you are out of HP, further damage goes to your WP. If you have any damage to WP, you take a -4 penalty to Strength and Dexterity, and each round you need to make a Fort save (DC 20) to avoid taking a point of damage from bleeding and such. If you beat DC 25 (or receive a Heal check DC 15, or get at least 1 WP of magical healing) you stabilize.
When you hit 0 WP, you pass out, and take 1 point of damage per round, with no save, and no chance to stabilize naturally. At -10 WP, you die.
WP heal at a rate of 1 per day. Magical healing cures 1 WP for each die of healing, so cure moderate heals 2 WP, in addition to 2d8+level HP.
For larger creatures, I've got it all figured out how to deal with it, but it's usually only an issue for PCs, since most badguys die, and it doesn't matter what their WP is. Note that most people, when they run out of WP, fall down and try not to bleed to death, rather than keeping on fighting. Thus, cleaving pretty much works the same way. Sure, a Goblin has an extra 5 WP beyond its HP, but it'll be 'dropped' for the sake of Cleave when it runs out of HP.
This does make PCs a bit tougher, while also making a dying speech possible, if there's no healing magic available.
Languages
I like languages, and I think just handwaving them away with tongues ruins a lot of potential for mystery and the exotic appeal of travel. Everyone starts with 3 ranks in their native language. Each rank in a language costs 1 skill point, regardless of class.
0 ranks - Practically a non-speaker. You might know one or two expressions if your character has expressed interest (e.g., one PC learned how to say, "Don't eat me," in draconic). Takes a -15 penalty to language-based skill checks.
1 ranks - Beginning student. Takes a -10 penalty to language-based skill checks. Simple sentences only, fluent enough to get around.
2 ranks - Fluent enough to hold normal conversations, but not a firm grasp on colloquialisms, idioms, poetry, etc. Takes -5 penalty to language-based skill checks.
3 ranks - Fluency of a normal person in that society.
4 ranks - Scholar-level knowledge. No bonuses, just props for being a cunning linguist.
Skills
Pick two skills that fit your character's backstory or personality. These are always class skills.
At first level, you get a number of bonus skill points equal to 6 + your intelligence modifier. These can only be spent on flavor skills, like Craft, Profession, and languages.
Classes
Multiclass all you want. I don't care for the favored multiclass rule.
Armor Proficiencies - You do not get medium or heavy armor proficiency automatically at 1st level. You must have at least two levels of a class that would normally provide medium armor to get that proficiency, and three levels of an appropriate class for heavy armor proficiency. This helps discourage dipping into Fighter for armor feats, and lets me have this next house rule. Of course, you can always just spend feats to get armor proficiency, if you're in a rush.
Armored Casting - Armor does not interfere with spellcasting at all.
Light Fighter - The light fighter is for folks who want a more nimble, duelisty kinda warrior. He gives up medium and heavy armor proficiency, but gets 4 skill points per level, and has Bluff, Sense Motive, and Tumble as extra class skill. You can't multiclass between normal and light fighter. Just pick one and stick to it.
Druids - Not all druids are Celtic-esque moon-worshippers, nor are they metal haters. They're just nature priests. They get light armor proficiency and simple weapon proficiency.
Stat Generation
Roll 2d46, drop the six lowest and assign three to each stat, in any order.
Action Points
At each level you get (5 + 1/2 your level) action points. You can spend an action point to add +1d6 to any d20 roll, after you roll the die, but before you know whether you succeed.
