Aw, man, I could really spend way too much time on this.
Dungeons & Dragons
D&D needs to decide whether or not it's a generic fantasy system, or a full game with a default setting. Personally, I'm pulling for system over setting. I'd redesign D&D to remove the setting-specific assumptions inherent in a lot of its mechanics--alignments as real, objective forces in the world, for example--and genericize the character system for greater flexibility: three ultra-basic character classes (with an optional fourth, if the DM wants to draw a distinction between arcane and divine magic), with a hell of a lot of feats and skills to customize them.
And, by God, it's got to be easy and math-light: D&D is the gateway drug of RPGs, and it needs to be able to hook people who didn't spend their youth optimizing their Magic decks. Feats should be organized into logical, thematic lists, each entry including simple language explaining why someone would want to take that feat (as opposed to giving us one sentence of nearly meaningless flavor text and then on to the numbers and fiddly bits).
The combat system also needs to be streamlined for the sake of newb-friendliness: Page upon page of special-case rules are a barrier to entry that this game does not need. Attacks of opportunity can be a lot of fun, but they definitely ain't for everybody. And, seriously, do we really need weapon lists that distinguish between eight different types of axe? Or between axes and swords at all?
Monsters would require a new system to make them just as flexible as PCs. "Level" would be the same thing as HD, ECL, or CR. Adding templates and class levels to monsters would be the rule, rather than the exception, and would of course be vastly simplified.
I'd keep most of the stuff that falls outside of the mainstream Western notion of the "fantasy" genre out of the core books--in terms of both PCs and monster options--but pour it on in the optional books. Supplements would be based on sub-genre themes or world elements. Instead of books of new stuff for arcane magic users or things to do in desert settings, there'd be books on steampunk, science-fantasy, sword-and-sorcery, biomancy, demonic powers, technomagic, alchemy, and so on. These would include the expected character options and monsters, and also optional rules variants to support campaigns of different genres and levels of complexity.
World of Darkness
Okay, I tried to do WoD, but it just turned into six paragraphs of me kicking White Wolf around. I've got other forums where I can go to be mean; EN World is where I try to be nice.
Short, non-mean version: My World of Darkness would be a more flexible game with less strict, setting-focused content. There would be much, much less emphasis on ancient, powerful organizations of supernatural beings. There'd be more room for your character to be something unique and unprecedented, instead of one more of a giant club. Character generation would be more freely point-based, with no race-class paradigm. "Metaplot" would be nonexistent, and game fiction would be minimal.
Also, "magic" would go back to the old consensus/paradigm/paradox bit, instead of the "wizards from Atlantis" business in the new Mage.
I'm going to stop, now.