Armin “Quark” Shimerman as “Mr Lovejoy” in the Married … with Children episode “Buck the Stud.”
Sharon Lawrence (“Amelia Earhart” on ST: Voyager) as “Linda Fusco” in the Monk episode “Mr Monk, Private Eye.”
Jonathan Franks plays a pedo in an episode of Criminal Minds.
James “Zefram Cochrane” Cromwell as “Judge Raymond Price” in the Matlock episode “Nowhere to Turn.”
Also in this episode is Earl Boen, the “Voice of Nagilum” in TNG, as “Judge George Clayton.”. He’s better known as “The Eulogist” on Seinfeld and “Dr Silberman,” the psychiatrist in the Terminator movies.
William “Commodore Decker” Windom (again!) as corrupted boxing promoter “Paul Mitchell” in the M:I episode “The Fighter.”
Also as imperious tycoon William Randolph Hearst in RKO 281, about the making of Citizen Kane.
Pamelyn Ferdin (“Mary” in TOS’s “And the Children Shall Lead”) as “Molly Mullin” in the Green Acres episode “Instant Family.”
Whoopi Goldberg (Guinan) plays Mother Abigail in the new adaption of Stephen King’s The Stand.
Bruce French (four ST appearances) plays a Medicare investigator in an episode of House which my wife just watched. Scroll down for pics here:
Probably already been mentioned, but I remember seeing Shatner in an episode of The Fugitive. I think he was playing a deranged killer.
What, again?!? 
A former cop, no less.
He played the bad guy in a movie adaptation of The Hound of the Baskervilles back in the day. Did pretty well in the role, too, as I remember.
This thread is so long that it may have been mentioned before without my being able to find it, but recently on YouTube I ran across an unsold pilot episode for a proposed Nero Wolfe TV series from 1959, with Shatner as Archie Goodwin, and Austrian actor Kurt Kasznar as Wolfe.
Shatner also played a murderer in an episode of Columbo. He was an actor who played a TV detective named “Lieutenant Lucerne.” His outfits defy description. Peak 70s is all I will say. Columbo would needle him by saying “Ah, that’s what you and I might think, but what would Lieutenant Lucerne have to say?”
Shatner played Mark Twain in one of the episodes of Murdoch Mysteries we watched the other day.
I’ve got to see that!
Shatner played a psycho bank robber and murderer in a syndicated Canadian cop show called The Professionals back in the '70s.
He was also the murderer in another episode of Columbo, “Butterfly in Shades of Grey” (1994)