I would like to see Kumungu, Rune Terra's 'spirit realm' and the Voodoo Lands (if it still exists in new lore) expanded into a fully fleshed-out official factions. Each region would offer a ton of new champion, lore, narrative and setting potential. You could introduce something like a new Aztec, Indian or Mayan-inspired civilization for Kumungu, make the Voodo Lands a hotspot for new and existing champions dealing in dark magic, and turn the vague spirit realm into the 'home' of spiritual or magic-based beings like the demons or Yordles (Bandle City now exists in some kind of pocket dimension that can only be accessed through a magic portal, after all.)
And if Aurelion Sol, Bard, the Void, the new Targonian lore and the new Dark Star skin line could be buildup for something more - then maybe Riot's planning on implementing a universal "cosmos" faction for champions that aren't native to Rune Terra? Seeing other aliens besides voidborn or even eldritch-terror space horrors as could make for amazing and creative champion additions to the roster.
In regards to existing factions - Targon, Bilgewater and Piltover's champ pools are still a little small and definitely need more additions.
And when it comes to factions that are overdue for a new champion, then the Void and the Freljord are overdue. Same with Demacia and the Shadow Isles if you don't count champion VGUs.