Spike and Drusilla(James Marsters and Juliet Landau) on Buffy, Seasons 2 & 3, before Spike became a regular.
Faith(Eliza Dushku), on Buffy and Angel.
Alfred Bester(Walter Koenig), on Babylon 5.
Frasier’s agent on Frasier – sorry, can’t remember either the character’s name or the actress’s name.
Harriet Sansom Harris, playing Bebe Glazer.
Carleton the Doorman
Anthony LaPaglia’s Emmy-winning turn as Daphne’s no-good drunk brother on Frasier.
Just hysterical.
Does Inspecter Lueger on Barney Miller Count?
Sidney on MAS*H, I don’t think he was mentioned yet.
Mama Carlson on WKRP
Someone said it already, but Buddy on Night Court was the Best.
Shelley Winters as the Grandmother on Roseanne was the best character on Roseanne.
On Northern Exposure I always like Chris’s Brother also but Adam was the best.
Lord John Marbury (Roger Rees) on The West Wing. He’s only in a few episodes, but very memorable.
Thanks – I was running through “Fifi, Gigi, Mimi…” 
Janice on Cheers. Yes, she was annoying, but Chandler wound up marrying Monica, who was even more annoying, and not as funny.
Friends.
Rex Harrison as Abraham Lincoln on Police Squad!
Seconded, and adding Mr. Morden (Ed Wasser).
“Feels like an Arby’s night”. 
Yay! I get to be first to nominate Harry the Hat (Harry Anderson) on Cheers.
David Cross on Just Shoot Me was great too. Now whenever we go through the bank drive-through: “Donnie says vacuum!”
Some good ones from recent/current shows:
Cliff the cheap lawyer on Veronica Mars.
Mandy on 24, just because we can gasp and say, “Omigod! It’s Mandy!”
The TSM on Lost.
And my favorite: The Mayor on Buffy.
Zapp Brannigan! from Futurama.
How they kept such a one note character so consistantly funny I don’t know, but they did.
“Kiff, I’m feeling the captain’s itch!”
“I’ll get the powder, sir.”
Kelsey Grammer on the Simpsons. Even if the Sideshow Bob episodes have failed in quality over the years.
The two guys who played the gay couple on “Barney Miller.”
The cigarette smoking man on the X-files. As time went on, to find out more and more about him was fascinating and chilling. One of my favorite episodes was when they told his life in flashback.
The man wasn’t evil, he genuinely believed he was doing the right thing.
I’ll third Bester, second Mr. Morden, and add Emperor Cartagia. I think they did a good job at starting him off as just a douchebag, and then slowly revealed that he is completly, fucking out of his mind.