As far as plot goes, I like having a type of guild as a "hub" since it provides easy plothooks, though if that ends up happening, I think downtime (adding slice-of-life stuff here) is important, too. Also, if you have multiple teams (some people perhaps staying home, others going out to one task, another group somewhere else), keeping everything distinct and clear is going to be a challenge. I do like it, though, it's just a challenge to keep in mind.
 
As far as scale is concerned, I like keeping the possibility of going around the entire country more than one region/city open, but I think having the entire world is a bit too much. Similar feelings on the power level, which I prefer more or less pretty restricted; nothing on the level of city block destruction, anyhow.

I guess this is more or less a given, but any kind of PvP is hard to pull off well and requires a lot of cooperation between GMs and players, probably more than can be expected if nobody knows each other (since well, there are no rules), so I'd steer clear from that no matter what ends up happening.