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.
'The Simpsons are going to...'
I wasn't watching regularly before that because of my job, but those episodes stopped me from watching for years. I used to watch every episode religiously with my family before going out on a Sunday night, and they just completely killed any desire to want to go back to the weekly watch.