A near future scifi setting would be nice, on that offers a goood contrast to the colourful fantasy setting of D:OS. And I wouldn't mind if there was an overworld map with freeform traveling between the hubs with random encounters ala Fallout and Fallout 2.
This I consider more important though:
More even focus on the amount of different content types. D:OS was great and the combat was really fun, but despite all the little things the player could do besides that, combat felt it was the main feature and for a massive game like D:OS the experience tends to get really heavy in the long run when lions share of it goes on doing combat, figuring out how to be better in combat, observing whether the upcoming combat situation is manageable, and recovering from combat.
Spread out the content and possibilities; more variety. More utility skills with quest and non-quest related uses, more quests that don't inherently or at all require combat, more ways of solving situations, all of which would lead to wider array of possible character builds. Let combat be as fun as it is in Original Sin, but let it also be just one of the features instead of "the" feature of the game (or, so it appeared to me). It remains fun for longer when it is more evenly paced and valued in-game with the rest of the content.
Also... More involving narrative structuring and writing.
Other than that, I can't really think of anything "big" to "change" for the next game(s). Aside from the above criticism of combat centricism, the general direction of Original Sin was pretty much spot on for what I look for in good cRPG. Just keep improving that formula.
