I dunno, at this point I can’t help but see him as Captain Rum from the Blackadder II episode Potato.
EB: There’s no need to panic. Someone in the crew will know how to steer this thing.
Rum: The crew, milord?
EB: Yes, the crew.
Rum: What crew?
EB: I was under the impression that it’s common maritime practice to have a crew.
Rum: Opinion is divided on the subject.
EB: Really?
Rum: Yes. All the other captains say it is, I say it isn’t.
EB: Oh, God. Mad as a brush.
To me, he is forever Det. Stanley Bolander, from Homicide: Life on the streets.
Neil Patrick Harris may not have killed his career playing Doogie Howser, but more people seem to remember his character’s name than his own.
I dunno, his role as what’s his face on “How I Met Your Mother” was/is pretty good. Probably isn’t the same kind of role, either, as presently he’s playing an egotesticle player who’s actually an okay guy some of the time.
This again? Hmm…
Since The Cosby Show, Full House, and A Different World have already been cited, I’ll nominate a key member of Murphy Brown, Charles Kimbrough. The remarkable thing, IMO, is that there never really was anything memorable about Jim Dial. He was pretty much just an uptight, cynical straight arrow (in fact, there was an entire episode devoted to how unremarkable a life he led). If anything, I expected Grant Shaud and Joe Regalbuto to get hit the hardest, and they’ve both had at least fairly respectable post-Murphy careers. For Kimbrough, it’s been pretty much just voices and bit roles.
How about Ellen Degeneres? Man, don’t know about her, but if I was in her position, that megahyped coming out on Ellen is definitely one I’d like to have back. Think about it: It was so huge, so publicized, that in her next major role, she played another character with the same first name (who’s also a lesbian, BTW). Crumbs since.
I’d like to give an special mention to Lorenzo Music for doing the opposite of the OP; it was his remarkable career that killed a role, the voice of the cartoon Garfield. Think about it: Why has there not been even one Garfield TV cartoon of any kind after the insanely popular Garfield And Friends? I’m almost certain that the reason Jim Davis insisted on CG for the movie is that he knew, in his heart, that replacing Music was just not possible. Note that the upcoming Garfield Gets Real is also going to be CG.
Other than the Professor Garfield website, I’m pretty certain that non-CG cartoon Garfield is long gone.
So you don’t know the way to France either?
Ralph Fiennes looks to be an interesting one. After Quiz Show there was The English Patient and more recently Lord Voldemort in the Harry Potter movies.
For your consideration, Jason Biggs in Jay and Silent Bob Strikes Back, making fun of himself:
Jason Biggs: I’m a teen idol, dammit! Don’t you recognize me? Look at me. I’m the pie fucker!
(Making fun, of course, of his success in American Pie and all its sequels)
Crumbs?
Ellen’s talk show won 15 Emmy awards in it’s first 3 seasons, won a few People’s Choice Awards, hosted the Academy Awards, got rave reviews for her voice of Dory in Finding Nemo, and her net worth is about $65 million dollars…
I’ll take crumbs like those any day!
This coinage was worth bringing a thread back from the dead. I laughed, I cried …
Reminds of one of jokes from Marc Price’s stand-up routine.
"It’s going to be on my goddamn tombstone after I die:
'Here Lies Marc Price
[pause]
Skippy, from Family Ties’."
Since that’s how he always gets introduced, no matter what he’s doing.
Oh, no… he’s had quite a successful career as a voice actor. He has done a brilliant Joker on all the Animated Series, and he’s been up for contention for the live action version.
You win the award for most apropos post in this thread. His serious work (pre-Police Squad, Airplane, etc.) was brutally good and he should be known as one of the great dramatic character actors of our time. Instead he is typecast as a bumbling idiot supported by a ton of sight gags.
C’mon guys, 193 posts in and no one mentions…
John Wilkes Booth. 
Three Words: John Boy Walton.
Surely you can’t be serious? wait for it
Wait, what? The actor who was only really known for Forbidden Planet and a Tammy movie was a great dramatic actor? What roles did I miss from this B-Level leading man? Airplane made him, it did nothing to hurt him.
I was just whooshed, wasn’t I?
Jim
How about Jerry Orbach?
Magnificent career, no doubt, but had he lived was he every going to be anything but Lennie Briscoe again?
I forget his name but the drill instructor in Full Metal Jacket
R. Lee Ermy.
However, he actually was a drill instructor before he got into acting (Oliver Stone had originally hired him as a consultant for FMJ but thought his demonstration was so incredible he decided to cast Ermy as Sgt. Hartmann instead). So it may be more that he’s playing the one role he knows best.
Although he was also good as the televangelist in Fletch Lives.
Edward Fox will always be The Jackal (yes, I know he’s been in other stuff, but whenever I see him, I always wonder at which point he’s going to try and assassinate Charles De Gaulle).
I know rather a lot of people who cannot think of Rowan Atkinson as anything except Mr. Bean, which is very disturbing…