Might be a hot take, but Mass Effect 2.

I love Mass effect, despite its flaws, but Mass Effect 2 was the game that derailed the series and basically forced Mass Effect 3 to have an unsatisfactory ending. So many concepts from Mass Effect 1 like the cipher, visions, Virgil, the Thorian were completely abandoned in favor of one giant video game length side mission. Sure the suicide mission was kind of cool, but at the end of Mass Effect 2 we learned almost nothing about the reapers from the last game.

But Cerberus is by far the worst mistake. From Shepard's POV, they literally witnessed Cerberus do grotesque, inhumane experiments throughout ME1 only a month before game start but the writers forced us to join these space Nazis. Cerberus is comically evil and is constantly doing cartoon villain experiments. Also, the space Nazis somehow have it in their hearts to spend billions of credits so that Shepard can save humanity.