Alright, Dave Grossman stated that the game will feature a crazy doctor, a pirate hunter, and a plot so huge and so evil that it threatens the heart of voodoo. Since we alreday know about the doctor and and hunter, I think the plot is more connected with LeChuck. A lot of what the voodoo lady said about LeChuck could match this plot and voodoo, about him having plundered his magic by not offering anything up to the voodoo world.
I personally think that LeChuck has made a very sinister and clever plan; dave and mike have said he will still be a villain after all. So this thread is just to speculate what this plan might be and LeChuck's remaining role.