Ever had a character, or worse a player, feel like Captain Meredith of the USS Mandela?
There's plenty of room for a new crew to do "great things" in a setting like Star Trek but one can still feel overshadowed. I know of people who won't play the movie era of Star Wars because the most important victories are on the screen. I know of even more people who resent canon NPCs in a non-licensed setting doing great things the PCs could theoretically do themselves. This here RPGnet thread got fairly grumpy in places.
It's up to the GM and players to deal with it, of course.
Quoting myself in the above thread: Being overshadowed gets pretty grating pretty quickly. The trick is generally not to upstage the PCs and always not to annoy the players.
Having Superman show up and save the day will undermine the heroics of a group of PC superheroes, just as it would the heroics of any other DC hero in their own comics. So look at how those comics' writers deal with it. Have a friendly NPC lend a hand, but it's still the PCs' victory.
Less overwhelming guest stars are likely to be less of a problem. When the young Wesley Wyndam-Pryce turned up to audit the PCs in TWH and was comically useless, the players were quite amused. When Rupert Giles visited for a session, he was wise and helpful but didn't overshadow them in action or investigation.
Canonical enemies are a different matter again. Players generally love to take a shot at a villain, and often prefer canonical cannon-fodder like Imperial Stormtroopers or Daleks to mooks the GM has created, as long as their abilities reflect their appearances in the licence.
One option, of course, is that the players play the setting's defining heroes. That relies on them liking and accurately playing canon characters, of course. I generally only do this in one-shots, although I make an exception for Doctor Who where there's plenty of precedent to make your own Doctor, and I'd try it in some other settings as well - Firefly with a keen enough bunch of players, maybe, since the stars are a classic adventuring party and there's little enough canon to toy with.
Edit: Another option as mentioned by Bill in the comments is to drop the canon cast and let a new group of PCs take their place. This is basically what is done every time you borrow an adventure idea, but done with a whole series, essentially using a show as a sourcebook. It doesn't really appeal to me as more than a thought exercise, though.