Can Larian really put a "destroy Vlaakith" plot in BG3? Remember, they do not have editorial control over the entire Forgotten Realms!
I think this is similar to Kaelyn the Dove's crusade against the Wall in Mask of the Betrayer... she couldn't actually destroy it no matter how much she (and I!) wanted to because that major a change to Forgotten Realms was not part of the purview of the title.
I have to imagine a plot to overthrow Vlaakith would deserve an entire game/book, and could not be a side plot.
Which is ironic considering WoTC quietly scrubbed mention of the Wall from canon relatively recently.
On the other hand, Storm of Zehir was used to introduce a new deity to the Yuan-Ti pantheon IIRC, and of course, the original Baldurs' Gate games used the Time of Troubles as a backdrop for its Bhaalspawn story, and eventually spawned the 'Murder in Baldur's Gate' adventure which brought back Bhaal. So I wouldn't put it off the table.
Descent into Avernus IIRC was supposed to be sort of a prequel to BG III IIRC. I wouldn't be surprised if there were some major story events were tied to BG III or vice versa. The story is already waving a bunch of important, high-level setting stuff underneath our noses in the early parts of chapter one. Multiple deities, the Nine Hells, the Netherese, Vlaakith, Spelljamming mindflayers, etc. It almost can't evolve into something epic and realm-shaking at this point, because it's already halfway there!