Now that the developers at Larian do not have to align their mechanical systems with D&D to get WotC job, they are free to go in any direction they want. So, I hope that they will take that opportunity to learn lessons from previous games and also go back to some of the great features of previous games. I personally find completely custom characters to be by far the most interesting way to play this style of game, so the ability to build characters from scratch has the most value to me.
I think the area with the most promise is the class system. The DOS games have had the most flexible approach, which actually I think has room for more definition. Although 5E might look like it has a hard class system, there are so many ways to customize it that it ends up being very open to player choice (multiclassing, subclasses, races, backgrounds). I would like to see a structured class system but with a high degree of customizability.
The combat system is one that I feel concerned about. The armor system in DOS2 was a major issue for me, and I hope that nothing like that will be repeated. I think the overemphasis on surfaces in the past 3 games was excessive and I would like to see it reduced. BG3 casters also felt weaker than in previous games, which perhaps was deliberate, but it would be fun to have some of the old spell effects again.
The magic schools in DOS1 were the most exciting to play, and offered the best ways to mix "skills" of different types in small quantities. The spell trees in DOS2 felt watered down and less fun in comparison. The spellbooks in BG3 were pretty good, especially considering the task of automating all of the interactions, so I hope to see a similar depth of spells, although not as many are necessary. If Divinity uses open magic schools again, I think the DOS1 balance between focus and diversity was the best one.
In the past three games, DOS1 was also the game with the best attribute system. Although it was the least similar to D&D, it was a deep system with many interesting ways to play, and rewarded players for building attributes and talents around skills. I hope for a return to highly customizable character features like that.
I am excited about the game!