Here's my POV for variant classes (and this goes for E6 and D&D as well).
The best way to use variants is to build them into the campaign world. That amplifies their mechanical coolness with something the player (i.e. human being at the table) can really jam to. That's what really lets those variants shine. So I think a great approach to designing a campaign would be picking say, six really distinctive classes, three distinctive races, and building the situation around that.
[sblock=Example of using variants to define a setting]Imagine an intrigue-filled endless "wild west" set a thousand years after the collapse of a victorian steampunk era (not severe magic chaos like eberron's last war, just a general decline in central political authorities and technological craftsmanship).
Gunslinger
(Ranger, no animal companions, must go ranged combat). Part of a brotherhood that has tremendous respect but very little political power. Code binds the gunslingers (i.e., must accept duels) but it's not alignment-based, so gunslingers can be on opposing sides of all sorts of conflicts. Code includes being impartial and sticking to the terms of a bargain. Non-gunslingers with guns are hunted down by the gunslingers, as are major violators of the code. Gunslingers must aid each other when someone breaks the terms of a gunslinger's contract. No weapons may be drawn in the presence of a gunsmith (gunsmiths are the non-combatant judges / craftsmen / trainers of the order).
Shaman
Setting's spirits are all incorporeal and unseen, but run the gamut from fickle tricksters to ancestor ghosts to nature spirits. There are also demons in the world, but they're your enemies.
Advocate
(Ninja-like abilities, esp. momentary invisibility and lethal strikes) Played as trained members of Houses, which are like crime families in a world with no police to get in the way. Imagine if rather than the Cavalry showing up, all you could hope for in the wild west was the arrival of the currently dominant local crime family. They are the political powers of the setting. These Houses span the setting - so if you make enemies of a House in one place, you've got enemies in lots of places. Houses know better than to try to acquire firearms, and they know well enough to hire Gunslingers when necessary. Advocates' secret fighitng style, including their ability to move undetected and make deadly strikes is passed from one generation to the next in a kind of assassin's apprenticeship. Advocates reach the highest levels of power within their Houses, although Advocates don't reveal that they are anything more than other gentlemen belonging to their Houses unless they have to.
Warlock
(Somewhere between the concepts of warlock and binder in D&D) You made the deal, maybe under duress, or maybe for good reasons. Now you get the benefits. There are many demons in the world, and they can be used... but they can use you too. What's important, though, is that you stay alive, because you're not looking forward to what's waiting for you on the other side.
Tetsujin (metal men)
Paladin Warforged. Played largely as-is (using stats for Warforged Paladins or whatever). They are found in some ancient ruins, and about a hundred years ago someone figured out how to wake them up. They don't know who they are, they don't know how they were made. Often this means they can be used by others, and they're sought after by the Houses.
Artificer
Primarily elans who are trying to revive the old arts, massively interested in the Tetsujin, highly uninterested in human politics and sometimes victimized by that disinterest.[/sblock]
