From what little I understand, (I may be wrong) elder brains can have personalities and that wouldn't break the lore. I don't think the problem is that the brain is the main antagonist, the problem is that, for all intents and purposes, it's not actually the main antagonist. It's more akin to a natural disaster, something faceless and mindless, a force of nature that has to be stopped and resisted, but that lacks a will of its own. It's a ticking clock rather than an antagonist we can relate to as a character. That role falls on Orin and Gortash, who are treated as secondary antagonists, lieutenants, barriers keeping us from dealing with the main threat. As a result, we the player end up lacking an antagonist we can really invest in for the length of act 3.
I think this issue becomes clearest if you look at the Dark Urge, the character who's most directly tied to the plot of the game. There, the netherbrain isn't really the antagonist either. Thematically, Orin probably fills that role.
