When you’re watching an episodic TV show (think Lost), who does everything happen to? The main cast.
And who drives the action when things aren’t happening to them? The main cast.
The same should be true in your campaign (which, in a lot of cases, resembles an episodic TV show more than most other types of media): Whenever something worth playing out at the table happens, it should happen to your main cast — the player characters.
Here’s the important part: It doesn’t really matter why all the cool shit happens to them.
Don’t get me wrong: It’s nice to have good, well-founded reasons that are neatly grounded in your campaign world and that fit logically into the overarching narrative that you and your players are collaborating to create. That’s an awesome goal.
But if you find yourself going, “Wait, why are the PCs the only ones who can do X?” or “Hang on, the last Massive Weird-Yet-Awesome Event™ happened to the PCs, too…” just stop, take a deep breath and do it anyway.
If it’s cool, go for it — that’s the heart of the main cast rule.
Do you agree with this principle, or do you take a different approach to putting the PCs into the thick of it?
(And on an unrelated note: It’s not too late to boss around the gnomes and tell us what you want to hear about D&D 4e from a GMing perspective.)