If we're talking High 2-A I am gonna have to shill my verse again since D&D is the only one with clear-cut villains out of my choices (mostly).
The Lady of Pai is my option for High 2-A despite how vague she is as a character.
While technically being neutral, she is neutral to such an extent as being antagonistic to many throughout the planes. She is the protector of the City of Sigil (the center of the multiverse) and is one of the few beings on par with Ao and other transcendent beings of the verse.
What makes her a villain? Well. For one, it is said that anyone who worships the Lady as their patron deity is instantly slain, or put into one of her infamous infinite mazes, trapped for all eternity. Furthermore, merely appearing in her shadow causes immense, indefinable pain from her existence. Opposing the Lady in any capacity causes a fate not dissimilar to the god of portals, Aoskar, who attempted to lace the City of Sigil with portals so he could freely enter the realm. He was instantly obliterated from the multiverse, made into an example of what happens when you attempt to defeat the Lady.
From a gameplay point of view, Lady has a few notable features in that she has no stats whatsoever. To some extent, every creature has stats- even greater gods, though they cannot be really killed unless under very specific circumstances, have stats. The Lady has no stats as this implies she can be killed or even vaguely affected by the actions of one such as a Greater Deity or lower.
She's even present in the game Planescape: Torment (an old D&D game we've been looking into) as A. the only one who can actually kill your protagonist and B. a small plushie doll that if you attack it or jeer at it, she shows up to literally obliterate you from reality because how dare you attack a plushie (apparently you can also get others to do this to summon her).
