Community: Professor Slater, who got between Jeff and Britta leading to the love triangle at the end of the second season, never re-appeared again.
Family Matters: Judy, one of the Winslow daughters, simply disappears after the fourth season.
Glee: Coach Tanaka, a major character in the first season, simply disappeared after Emma declined to marry him.
Spin City: Connie Britton wasn’t yet “Connie Britton” but she was adorable on “Spin City.” However, when Michael J. Fox left the show and Charlie Sheen took over as mayor, Britton’s character Nikki (as well as two other major characters) didn’t make the transition for unexplained reasons.
West Wing: Mandy Hampton (Moira Kelly) was never written out of the show; she simply disappeared after the first season.
Scrubs: Dr. Grace Miller was written in the show as a female counterpart to Dr. Cox and then, without explanation, disappeared.
That 70s Show: Tina Pinciotti (Donna’s little sister) was around for a few episodes, but dropped. Later, Donna was referred to as a single child.
A Different World: I had forgotten that Marisa Tomei was even on this show, but when Lisa Bonet left, so did Marisa Tomei’s character, again without explanation.
Friday Night Lights: Remember Santiago? He was in 11 episodes. Where’d he run off to?
Heroes: Monica Dawson, the vigilante waitress whose superpower was as a muscle mimic, was introduced in season two and disappears without explanation in season three.
Lost: I believe there were several, but one of the most prominent was Isabel, a high-ranking member of “The Others” who also disappeared without explanation (though, Lindeloff explained that she was dead).
Bones: Dr. Goodman was a major-minor character in the first season, but doesn’t return in the second season. It’s explained that he’s on a two-month sabbatical, one that he still hasn’t returned from, apparently
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