Here are the issues for me:
First and foremost, stability and performance. Crashes, lag, sound-cutting out, bugs that prevent progress (still have two characters who can’t get past the drop-pod area on Promethea), bugged enemies who prevent progress/are unkillable, etc.
Bugs, bugs, and many other bugs. More new content, more bugs. I’d rather have less, that was more stable and better. This goes double for drops.
Majority of the modifiers are not fun for me, so I spend a lot of time “farming” for a playable set for my build/group. No way to “lock” modifiers or save them between Mayhem levels and play modes (single/co-op/normal/TVHM).
Majority of the drops are unexciting, under-performing pieces of garbage. So it takes a while to farm for something useful. Especially if it’s from a boss, where restarting the game takes longer than the fight.
Majority of the anoints are mediocre at best, so even if I found the right weapon, chances are the anoint will be useless or counter-intuitive (Dictator with jump/slide anoint).
Guardian Rank system has many issues, from the time it takes to assign points, to the choices, to the diminishing returns, to just adding more numbers instead of new options (though the Slam perk is a nice step in the right direction).
Inventory management is terrible. More storage, more gear, same horrible UI to try to find what you have. We need search/filters, and ways to partition storage for each character. We need a loud-out system to store gear and skill choices for easier build creation and modification. Trading is also a bear. It’s easier to just drop gear on the ground than use the UI, unless you need to transfer money, or are on Sanctuary where gear will just fall through the floor. Yes, you can use the table, but that’s not the solution we need. Eridium is useless after a while, yet you can’t trade it.
Some mobs are worse than bosses and not fun nor rewarding to fight. Looking at you anointed militant. But some NPCs are even worse than these mobs. Looking at you Pippie (#PippieMustDie).
This is a brief list, based on the multiple-dozen tickets I have submitted trying to get the game playable.