Heroes - The first season finale was the chink in the armor.  By the time Season 2 ended, I was wondering if they were flatly trying to turn people away.  Characters showing a glaring lack of intelligence, all too noticeable plot holes and what I attribute to believing its own hype killed this for me.  I couldn't care less what the hell happens to any of the leads.  I thought I'd make 3-4 episodes of this season before deciding whether or not to keep watching.  Then, news of Claire's girl crush (or whatever) came up.  I made it through the premiere and promptly hoisted my middle finger.
Smallville - The last time I made a point to watch was the season finale when (what they claim was) Bizarro flew off.  Truthfully, that was too long.  So much wasted potential.  What started as a promising vehicle, giving insight to Clark Kent's maturation, turned into a transparent, banal and repetitive exercise in simply cranking out 22+ episodes instead of keeping a tight narrative.  I just got sick of being pissed off with the show.  When you start rooting for prominent characters to die, it's time to go.
Nip/Tuck - Cripes, I used to love this show.  The Carver fail unnerved me, but ultimately it all got waded in too much crap; Sanaa Lathan, J.R. Ewing and the Organ Harvesting Quasi-Lesbian was the writing on the wall.  I managed to endure the pointless move to L.A., but haven't bothered with this season.  Nip/Tuck used to be great at making me say "Damn.  That's messed up." ...in that good way though.  It began to come across as if the writers were trying to try too hard.  I might actually be able to get back into this at some later point.
Brothers & Sisters - The combustible family dynamic was heartwarming and entertaining at first.  At some point, it became nauseating.  I started questioning why these people weren't housed in an asylum somewhere or at least being forced to seek therapy.  ****ing dysfunctional loons.
Grey's Anatomy - Seriously, just show me the episode where they take a group outing to get tested for STDs.  When the bedhopping and boinking overshadowed any hint of character growth or plot synthesis, I was gone.  That turned out to be when Izzy started ****ing a ghost.  I still don't know what that was all about and I don't care.
FlashForward - You had me real excited for 2-3 episodes, ABC.  Better luck next time.
SportsCenter - I used to LOVE this thing.  What the **** happened?!  It was creative, clever, timely, informative and just flat out entertaining.  I'd be able to watch the same show 3-4 times in row when they had the early morning repeats.  Now, I can't stand it.  I don't know whether it's the goofy formats or the emphasis on trying to be a entertainment vehicle, but I rather watch ESPNews or just browse the website if I need sports info.
I could probably come up with a few others, but thinking about the dreck that Smallville became has me all angsty and I need to find another topic.