In two words: Charlie Sheen.
Say what you want about Charlie, and Lord knows there's a lot to say, but he's a significantly above average actor, especially as a comedian.
Lou Costello, praising Bud Abbott, famously said, "Comics are a dime a dozen, but good straight man is hard to find." Sheen was/is a decent comedian, but he's an amazing straight man. Go back to the first few seasons of 2.5 Men — I have almost no knowledge of the timeline on Charlie's personal demons, but, like Matthew Perry, his later work suffered — but in the early years he could accomplish more with a deadpan or confused silent stare than most major comics can do in a thirty minute monologue.
Once Sheen left the scene — again, no idea how bad his personal issues were — the show lost its moorings. Ashton Kutcher, his supposed replacement, is a below par actor. Call him an 8 handicap, and played an unsympathetic character. Who is going to identify with an emotionally immature billionaire with a private jet? Courtney Thorne-Smith played an increasing role, but is similarly a below replacement level actress whose character was an indifferent, screeching, alcoholic mother.
Moreover, good actors like Holland Taylor and Melanie Lynskey (a Kiwi!) essentially disappeared from the show. They played flawed characters, to be sure, but were spot-on at it. Instead the show kept introducing half-baked characters who never broke through. Amber Tamblyn was okay for a while, but never really took, and the guy who played Barry was a joke, and not in the good way. The child actor who played Louis was nothing more than a throwaway. I hope he's overcome the experience.
Instead we were left with hours of Jon Cryer cringe comedy. Seriously, do any of us need another scene of Alan Harper in a neck brace? The absolute low point of the series was in Episode 6 of the penultimate season when Lynda Carter guested as herself and Alan made a complete fool of himself as a rabid Wonderwoman groupie. You can admire Cryer's commitment to do anything for a laugh, but eventually cringe comedy is just cringe.
So fare thee well Charlie Sheen. You are missed.