I can’t imagine the Carol Burnett Show without Carol Burnett. 
I nominate Ed O’Neil as Al Bundy. He bought something to the role that no one else could have, and easily carried Married with Children. Peggy was a trailer trash shrew without many unique qualities. Kelly’s function was to look hot and act stupid. Bud got better as he got older (the “Grandmaster B” stuff was hilarious), but was pretty generic early on. The only person who came close to Al was next door neighbor Steve, who I always thought was vastly under-rated.
Coupling without Richard Coyle (“Jeff”) would be complete garbage, and infact it was when he wasnt a part of the cast after the third season.
Deadwood without McShane would not have been a fraction of the show; those “cocksucker Shakespearean” soliloquies and rants held it together and I can’t imagine Ed O’Neill (the original choice) or others delivering them in such a way that you can simultaneously believe 1) this is this person’s natural way of speaking 2) this person is capable of cutting you into ribbons with a fingernail file if he feels the needs 3) this person is by and large sane and not totally evil.
Since there was name-only comparison between the historical Deadwood figures and those on the HBO version they could have written out Seth Bullock, Alma Garret, or any of the other star characters, but without Swearengen, no show.
Although only a few shows have been broadcast, there’s not a doubt in my mind that Castle would be unwatchable, were it not for the wonder Mr Fillion.
Star Trek: TNG would’ve been canceled faster than the original without Patrick Stewart. Dorn and Spiner couldn’t have kept it afloat on their own, and the rest of the cast was pretty much riding along with the three of them.
3rd Rock from the Sun would not have worked without John Lithgow. While everyone else was good, Lithgow made the show great.
Newsradio is the perfect example for this OP.
Tremendous ensemble cast (maybe the best ever), but when Phil Hartman died, the show was finished.
This is the textbook example of the OP’s thesis.
That also applies to “8 Simple Rules For Dating My Teenaged Daughter” and John Ritter.