So this new World of Darkness thing and my pre-existing obsession have combined, Voltron-like, into something new and horrible. What if I ran a World of Darkness city as a sandbox? Or at least something sandbox-esque; Vampire, Mage and the rest lack levels and treasure, but there are a few principals besides "run around stealing things" that I could loot for a game run with such a system.
Most specifically, the idea of having a large, irregular player pool and allowing more than one character per player appeals to me, and wouldn't be too hard to implement in a dark urban fantasy game. I'd just make sure that the action ends by the end of the session, so the next one can start at the local nightclub or whatever else the game uses as its tavern-equivalent. With that policy in place, scheduling becomes a lot easier, since I don't have to worry if a couple people can't make it, and it would be easy to introduce new players and include people who can only play on an occasional basis.
On the other hand, I'd have a whole lot more characters to keep track of--more plans, goals, family members, rivals, and NPC reactions, not to mention more factors to work into any NPC plots and plans, if I go in for that sort of thing. My main thought right now would be to rely heavily on maps. Get a map of Washington DC, or a couple specific neighborhoods, and mark it up with the places various characters have been, then key in all the people they've pissed off. Planning for the future wouldn't be too much of a problem; so long as I could keep a good handle on what's out there and what's already happened, I can figure out how to react to whatever weird plan the PCs come up with during play.
I'm not sure it'd really end up being all that different from a normal nWoD, just with stronger emphasis on setting and how the characters interacted with that setting than on any particular player groups grand story arc. It's unlikely that I'll find out any time soon, since I'm still happily working on my Swords & Wizardry sandbox and I've got plans to run that all next semester. But it might be a fun thing to try, if I ever give into the lure of those wonderfully shiny books.