As a GM of P&P games since 1984, I thought I would share some thoughts:
Every good GM knows that you spend litterally thousands of hours preparing the setting for the players. Hence, the option to preplan and save an area in D:OS2 should be implemented.
It is also highly unlikely that you will be able to insert intelligent NPCs in such areas, and let the player communicate with them. Merchants and such, yes. However, inserting hints, tips and clues should be no problem. Parchments in chests, writing on walls, etc. I guess this is already in the plans.
One of the flawed but extremely useful systems in AD&D, was the Random Encounter chart. A similar system could be easily adapted in D:OS2. Let the game decide if there should be any encounters in an area whenever the players decide to go walkabout, and let the GM launch it with a single click. Of course this should be adapted to the player's current level. One of the flaws in the AD&D system was that the DM could roll up a Red Dragon for the first-level players, killing the party in one turn.
This also launched the term "Random Encounter Quest," where the players just walked into the wilds with hopes of finding monsters to raise their XP. The P&P version of grinding, and a huge headache for any GM who wanted to move the campaign forwards. You plan every major encounter in advance, and then the players just swat them aside because they've spent a week massacring Kobolds. No fun at all.
Exploration, riddles and traps is the backbone of any decent P&P campaign IMHO. The problem with crossing a river, or opening a door. This is much more important to me as a GM than slaying monsters. Implementing a system for this will be vital. Ballance is also important.
On the question of how to adapt this system to the main game, it's actually quite simple. The GM creates a side quest/campaign, and at some point in the main game, played in GM-modus, the players get sucked into it. Look in the wrong mirror, open the wrong door, move a barrel to find a trapdoor to the Underdark. Playing the main game in D:OS2 in GM mode just as easily do this as it's done in P&P games. It's basically a question of letting a GM create their own micro-campaigns.
This also creates an absolutely brilliant possibility for community interaction, but that's something my head hasn't quite gotten around yet.