I believe that a setting must have credible villains. Villains, like heroes, can be flawed. They can and often make horrific mistakes. (As a rule, perhaps using history as a guide to see how people can make mistakes. Evil rulers can often prove to be their own worst enemies.)
I think one of the weaknesses of the 2nd Edition Realms, besides those mentioned in this thread, was that it often seemed that the NPCs were running the show and the PC heroes were just along for the ride. Now is the time for new heroes to arise in the Realms, using weapons, wits, and magic to shake the counsels of the high and mighty. Perhaps PCs in your FR games will be the ones to succeed in removing a major threat. Would that violate canon? Yes, but I think that we should remember that each group makes different uses of a setting. Mind you, I think that some threats might be eliminated in a 4th Edition Realms book and others arise. Perhaps to reflect the tumultous times, a new book could feature some new NPCs -- whose deeds may inspire the PCs.
(Perhaps that is part of the grumble about Elminster and the Chosen -- before the FR novels, little was known of the deeds of those NPCs. I would like to think that the deeds of an NPC are a bit more interesting to most DMs and players than their statistics.)