Deus Ex: Invisible War. It might have been a symptom rather than a cause, but it was a clear example of how the PC was sidelined as a game platform throughout the 00s, and the simplification of genres traditionally found on PC for console hardware.
Also, on an individual level, the game sucked! The original didn't have the best voice acting, but it was hammy and endearing. Invisible War's was somehow just wooden and boring. The levels were cut up into tiny chunks separated by loading screens, but even as a whole were smaller and more claustrophobic than almost anything in the original. The weapons were less fun (universal ammunition??), the inventory system was gimped, menus were all big and slow to navigate, stealth mechanics were oversimplified, there were fewer notes and logs and books and news articles in the game world... You get the idea. It's honestly a miracle that the franchise ever recovered.