With another edition here, I'm thinking of character concepts that are now more possible than before without having to ignore or houserule a bunch of material, because of things like certain concepts being more at the forefront or the removal of multiclassing and alignment restrictions.
The first thing that comes to my mind would be a Great Old One Warlock with a pact to Neth the Plane that lives. I feel that Neth would certainly be within the same category as their examples of Ghaunadar, Tharizdun, Dendar, Zargon and Cthulhu. A Warlock of Neth I feel would be tasked with trying to learn more about the outside Multiverse for Neth as one of it's eyes and ears. Once the Warlock gets Create Thrall, I think it'll want the Warlock taking victims to the plane itself so it can absorb them. And maybe after absorbing and learning more about the planes itself, Neth will learn of something that might be a threat to its existence.
The second thing that comes to my mind are Paladins with the Oath of the Ancients, which is pretty much the Neutral Good Oath with a strong nature and Fey theme. I could see one of these Green Knight Paladins connected to the Beastlands rather than Feywild, with a quest to hunt the Wild Hunt or the Unseelie Court across the planes fighting it's corrupting influences on nature. Or having the difficult task of establishing a pure enclave of nature within the urban sprawl of Sigil itself.