I'm expecting (like many others) the players' side to be largely the same - but the DM's side to be overhauled. And we already have something approaching my single biggest wish, the spellcasting monsters being overhauled so they don't really use PC rules.
On the player side there are the obvious changes. Artificer goes into PHB. Ranger is replaced either by the Tasha's ranger or by another iteration. Four Elements Monk and a couple of other subclasses are re-written. With luck they'll overhaul the Warlock invocations and either edit or replace all the "add a spell to your spell list" invocations for more interesting things, and give the level 12+ fighter some abilities that aren't repeats of lower level ones (and do more for the level 12+ rogue). Also the sorcerer subclasses being buffed to Tasha's sorcerer level.