Most of the time, a show approaches its end painfully slowly, especially if it has a large following. Similar to The Simpsons' shift from humor based on the show's plot and characters to the world outside Springfield, other shows' declines are marked by a decline in storylines. As characters are paired off, suddenly become friends, have children, or, in the worst cases, are placed in deadly situations or outright killed, the tension that drives the show starts to fade.
Of course, there are exceptions. In Desperate Housewives, for example, I think the writers are required by contract to include at least two murders per season, one extramarital affair, an assortment of other crimes such as embezzlement and arson, and somehow keep all the main characters in the neighborhood. In Law & Order, at least one person is killed per show, and every so often the assistant DAs and main detective's partner get changed.
Then there are shows like Grey's. While Grey's has so much emotional tension that it's surprising no one's been murdered by a fellow colleague, the last two seasons have stretched the limits. By the fourth season, though, almost all of the interns had passed their exams. However, rather than continue following the tension between these new residents, the older residents, and attendings, a set of new interns was introduced. Rather than having interns who were interesting, the interns were presented as one-sided fools.
Come fifth season, the drama gets ridiculous — the interns practice stitches and putting in IVs on each other because they only see the residents for five minutes a day. One intern has her appendix removed by the others, and almost dies, and is later dismissed from the hospital. None of the residents are punished. And the cherry on top? One resident, Izzy, sees her fiance's ghost, and later finds out it's a hallucination caused by… (schizophrenia? a strong prescription medication? sleep deprivation?) a rare stage 4 brain cancer that may kill her in three months. If that's not a writing disaster in progress, I don't know what is. One of the main characters is leaving at the end of the season because the actor didn't renew his contract. Losing a second main character seems like a really, really bad idea.
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