For me it was Lisa Goes Gaga. It was focused entirely on Lady Gaga who played herself and was awkwardly inserted, I don't mind the occasional brief celebrity appearance or when they lend their voice to other characters (ex. Meryl Streep playing Jessica Lovejoy in Bart's Girlfriend) but they started to feel so forced. I tried watching the occasional episode afterwards but people like JJ Abrams would show up in Do PizzaBots Dream of Electric Guitars? and I'd lose interest.
I have started watching the show again but I am curious who else has lost interest due to an episode or trend especially those who have been watching the show since its beginning.
IIRC after the writers left they applied an algorithm to measure ratings against character involvement, and Bart and Homer were the standouts, and so there was top down pressure to limit episodes that didn't revolve around Bart and Homer.
I admit that they already were the primary subjects of most episodes before that, but it became even more pronounced later on.