I wouldn’t call the whereabouts of past characters major plot holes. I’d like to know where they are now, but that’s character specific and not necessarily important to the main story.
Why was the destroyer so small and how were we able to kill it so easily? There have been fan theories for years, for so long that the once biggest question got dwarfed by the events of BL2.
What and why are the guardians? We had a vague idea of their purpose and we learned of their origin in TPS, but now we have a lot of Guardian lore, where before they were largely a mystery.
What even are the vaults and why do they exist? Again we had a rough idea, but more of their history and origin has been uncovered, particularly the vaults featured in BL3. I, for one, did not see that coming.
What is the Siren connection to the vaults? Now we know. We still don’t know of their origin, but it seems that’s a mystery of the Borderlands universe and I’m okay with that. We know more about how their powers are transferred. Again, did not see that coming.
What happened to the Eridians? Now we know.
Where did eriduim come from? Okay, we can only piece together what it actually is and what it does, so that’s not totally complete, but we at least know something about other than shiny purple power crystal thing. But not much more than that.
The only things I must know are, what was Commandant Steele’s Siren power and who/what was “The Watcher” in TPS. It wasn’t even mentioned in BL3. I’d like to know more about Steele, but again that’s character specific lore.
TPS wrapped up how Jack knew about The Vault of The Warrior, BL3 wrapped up the events of BL1. I’d say that’s case closed, the rest are minor details. Don’t get me wrong, I’d like to know more, but there are no big unanswered questions.
If there is a BL4, I’d expect it to be a new story altogether. BL3 satisfied my questions about plot holes in the lore of the Borderlands universe, and there are still DLCs to come.