I echo what's been said about the "mandatory romantic subplot" thing, but that's not a killer for me, it's just an annoyance.
On a general level, something that usually loses me is sexual stuff. It can be done well if it has meaning or it's played for laughs. Stuff like Persona 4 and Bayonetta are great examples, and I love them both. But more often than not, it's just crowbarred in there because people think if it has boobs it'll sell more. Frankly I just find it gross, insulting, and usually quite sexist.
For a specific example, anything they've done with Metroid since the end of Prime 3. All of Other M's faults, putting the franchise on ice, not letting Retro work on it, putting Other M Samus in Smash 4, FREAKING FETISH SHINY LEATHER ZERO SUIT WITH BEAUTY MARK AND ROCKET HIGH-HEELS ARE YOU SERIOUS?! To quote Spoony, "I just get a little emotionally invested in the series, and I just want it to stop sucking!" All it would take is for them to ignore one insignificant and awful part of a long and great series, but they keep insisting on pushing it into the limelight, and I seriously do not understand why.