Some side-quests should be locked when story progresses

As usual, quest givers and other NPCs will talk to you during side-quests, except it doesn’t make sense when those characters were killed (e.g. Calypsos) or, to a lesser extent, captured during the story (e.g. Tannis).

I think the whole thing would look better if there were some points of no return after which some side-quests would be disabled. It’s not like it would be much of a problem for completionists because you have more than 1 playthrough and ultimately you can reset your progress in TVHM anyway.

The Calypsos respawn like other bosses, right?

Yes but that’s not the issue. There is that very important character that will sacrifice at the end game. Elspis is modified in post game and the COV radio mentions the death of Tyreen and Troy. It gets a little weird when you do quests like Capture the Frag where they both talk to you when in reality their deaths already affected the game’s environment.

It’s no stranger to have them talking to you than it is to actually face their physical incarnation again. People certainly shouldn’t be able to farm Graveward since it’s intrinsic to the story that it’s permanently destroyed. There are all sorts of discontinuities that arise in the name of gameplay.