Seinfeld was the original show about nothing, of course, but I don't see any reason that other shows can't adopt that same mantle.
Seinfeld was a show about nothing because it rejected premises. Just by comparison, Cheers was a show about a bar. M.A.S.H was a show about doctors in war. Growing Pains was a show about the difference between the practice of psychology and the reality of family life. Mr. Belvedere was about a butler. And that brings us back to Seinfeld. In the Seinfeld episode explaining the show about nothing, Jerry and George end up making a fictional show in which comedy is supposed to be created by the fact that a judge sentences a man to be Jerry's butler. That is a premise.
Four friends in New York and their daily travails is not a premise. One critique I saw of Seinfeld said that the show was based on Jerry Seinfeld's personal moral code--a code about politeness, civility, and how people should interact with each other. That seems to be true as well, but it's still about daily life and there is no underlying premise that you have to buy into--there was no artificial background fact that forced these four main characters to be around each other. It was just four people who liked each other.
The Simpsons has reached this point too. It started out as a Honeymooners knockoff designed to comment on the American family. In the first three seasons or so, Homer and Marge cared about teaching and instructing their growing children. Every once in a while, Homer would suffer some real angst and actual regret. As it became more established, the show changed significantly. The family stories were still there, but since the show had covered so much ground, the family got pushed to the background while pop culture and satire moved to the front.
The perfect example of this is the episode in which Homer is hired by an evil mastermind to help bring a nuclear reactor online. After moving to a new town, Lisa finds she is allergic to nature, Bart is held back in school, Marge has nothing to do all day since the house cleans itself. Homer is happy in his new job, but ultimately chooses to move the family back to Springfield to make his family happy. That's a great story about the demands of family life, but the B story really makes the episode special. In the background, we have Mr. Scorpio, a Bond style villain who is also a New-Age boss who tries to make the work environment fun. It works as social satire about the stupidity of making office work fun and as a long form pop culture reference to the Bond films.
From this point, the show for a brief period went very far towards pop culture references. But that ground was ultimately taken up by Family Guy. On the other side, King of the Hill took up a lot of space about simple family issues. The Simpsons was left the middle ground and a slew of well established characters from the whole town.
And that is why The Simpsons is a show about nothing. At this point, Marge, Homer, Bart, Lisa, and Maggie are a family only nominally. Any new episode will essentially be about four and a half people who happen to live together, but without any particular relationships between them. It doesn't really matter that Marge and Homer are married or that Homer is Lisa's father, or that Bart is Lisa's brother. They just happen to live together.
It's not necessarily a bad thing. If you go into an episode with this in mind, you will probably be more satisfied than if you thing it is still about the American family.
