julia karinsky/ mazzonne -caroline in the city
mel-frasier
emily- friends
wilhelmina slater- ugly betty

Some favourites and an honourable mention to all the villains from the 60s live action Batman (http://www.sitcomsonline.com/boards/forumdisplay.php?f=363) series.

Maj. Hochstetter and the not so villainous Col. Klink - Hogan's Heroes (http://www.sitcomsonline.com/boards/forumdisplay.php?f=71)
Officer Kirk - Happy Days (http://www.sitcomsonline.com/boards/forumdisplay.php?f=12)
Siegfried and The Claw - Get Smart (http://www.sitcomsonline.com/boards/forumdisplay.php?f=142)
Wilhelmina Slater - Ugly Betty (http://www.sitcomsonline.com/boards/forumdisplay.php?f=682)

Louie De Palma on Taxi was sort of a villian too.