Okay, cool. I need to give a caveat at this time: I have not read the Neverwinter book, though I have watched the trailer.
Okay. Think post-apocalyptic. The trailer makes it clear that Neverwinter has suffered badly in the Spellplague and since.
Now, one of the major themes of post-apoc seems to be "community building" - the chance to make things better. So:
1) Identify a smallish starting community for the group. This may be Neverwinter as a whole, or it might be some part of it, depending on just how broken up the city is.
2) Identify the things that the community needs. Food? Fresh water? Security from predators? An end to the magical plague effects? Try to come up with half a dozen things.
3) Identify the factions that prevent access to these things, or that just pose a threat to the community. Maybe the bandits have access to the water supply. Maybe there's a local necromancer who keeps stealing dead bodies.
That should of course populate your sandbox, and also give you some easy starter quests. As for intrigue...
I would suggest starting the group with contacts amongst either (or both) the Church of Torm or the local Druid circle. Have them be the 'go-to' sources for starter quests, or for when the players don't have ideas of their own.
I would also seek to tie the PCs fairly quickly into the local political scene - have them do favours for the local lord/council, or whatever. Preferably have each of these patrons tie in to a different player, perhaps with one or two players 'unaligned'.
And then put the various patrons at odds. Perhaps the Church of Torm has chosen to site their graveyard in a region sacred to the druids. Perhaps the local lord has fallen out with the high priest. And, of course, all of these factions should have some sort of corrupt elements within.
And there it is.
Oh, one more rule of thumb I find useful when creating campaigns of this sort: "The PCs are rock stars." That is, the PCs very quickly become known and loved in the setting (even if they're loved for throwing TVs out of windows, or other outrageous acts). So don't tie them down with mundane nonsense, but do surround them with groupies, venal managers, corrupt would-be agents, and all the like.
Anyway, I hope that helps. Sorry I can't be more specific; as I said, I haven't read the book.
Thanks delericho - post apocalypse/community building is a good idea, as is faction conflict.
I'm starting to think though that I may want to loot the Neverwinter book for stuff I can use in my current Loudwater setting; notably the Factions, several of which aren't particularly Neverwinter related. The Netherese in particular seem to fit in better in Gray Vale than in Neverwinter! Certainly my players & I love Loudwater right now and I wouldn't want to involuntarily uproot them.