Charlie’s Angels tanked after Kate Jackson left. 
Gilmore Girls. After about season five, the writers were just thinking of dumb decisions for the characters to make in order to spin out the show as long as they could.
LOST, for so many reasons we’ve gone into many many times.
It’s so sad. I loved that show in it’s first 3-4 seasons. I couldn’t wait for it to be complete so I could watch and enjoy the whole thing over again.
Then it descended into… mush.
I’ve never been able to bring myself to watch any of it ever again. So, so disappointing.
Married with Children really went down the crapper towards the end, particularly the last season.
When I read the title of the thread, I thought Heroes. It’s the epitome of the phenomenon. Oh, Glee started off great in S1 and got progressively worse as well.
Scrubs decided that the wonderful capper to Season 8 wasn’t a good enough sendoff and proceeded to run electricity through the corpse to produce the zombie Scrubs Season 9.
Also, The Office didn’t know how to end itself after Michael Scott left and proceeded to meander through some not very interesting new charecters until it finally ended in a whimper.
The final season of That '70s Show. Everybody tried, even Josh Meyers, but without Topher Grace, there was no one to play Charlie Brown, if you get my drift.
Season Two of Heroes was devastated by the writers’ strike. Once the strike ended, they were only allowed to produce 11 episodes, and they tried to shoehorn all kinds of stuff into those eleven shows.
Twin Peaks.
I don’t think any other show comes close to The Andy Griffith Show after Don Knotts left. He was the heart and soul of that show. I think there may have been only one half-decent episode after he left. That show was dead on its feet for like 3 seasons after he left. I could never understand how they would continue to make such terrible, terrible episodes season after season.
Another vote for Dexter. The first 3 or 4 seasons were really good. It went steadily downhill from there until the awful last season and series finale.
Land of the Lost - a 70’s childrens program. 3rd season the Dad left and they brought in Uncle Jack. The writing became poor, Chaka could now speak english, the plots too weird.
It’s a Showtime thing. Show me a Showtime original and I’ll show you a good premise, very good first couple/few seasons, then fall off the cliff: Dexter, Homeland, Weeds, Nurse Jackie, Californication, Borgias, Tudors, Masters of Sex, etc…
The only exceptions, for my money at least, are Shameless and Episodes.
The good thing about Heroes Reborn being dreck is that we now know it wasn’t the strike that sent Heroes careening off the rails. We no longer have to lament what could have been, because season 2 and forward were always destined to suck, strike or no. Season 1 was a wonderful aberration, we just didn’t know it at the time.
So another vote for Heroes as the poster child for TV shows that nosedive.
The Battlestar Galactica reboot was pretty bad in this regard too, IMO. It still had its moments after season 1, but I think season 1 was just so good, that the drop off to “meh” levels is pretty noticeable. I admit that it’s possible that the ending was so terrible that it’s clouded my view of the rest of the series.
Can’t believe that no one has mentioned Prison Break so far. The quality of the show declined rapidly after the first season. And then, in its final season, just when everyone thought it couldn’t get any worse, it took a spectacular nose-dive. It got so terrible that I stopped watching just a few episodes before the series finale. By that point I didn’t care any more how it ended.
The last two and half seasons of Malcolm in the Middle, was quite terrible.
American Crime. Started well, then tanked around episode 4 or thereabouts. Now, is genuinely terrible.
As mentioned, Lost.
House MD. I remember being glued to the TV binging the first 2.5 seasons when I discovered it, but at some point the medical stuff become background noise and the interpersonal stuff lost any relationship to reality.
But the worst was the new Battlestar Galactica. The first two seasons were very cool, but then all the religious nonsense kicked in and it became painfully clear that they didn’t “have a plan”.
Lost and BSG made me swear off mystery-based TV shows.
The original Doctor Who. It went from great to bad at the exact moment Peter Davison left.
The new Doctor Who, big drop in quality about the time David Tennant left. I still watch it, but it’s not as good.
I’ll second this. Twin Peaks started decaying almost at once, but the pace accelerated as the show progressed, and by the end it was pretty awful.
I’d also nominate Northern Exposure. The show was amiably wacky and always tried to defeat common expectations, but in its last season it became almost like any other show on TV, and the characters were acting like stick characters, not the well-drawn weirdos we’d grown to know and love.