Blackwarder
Adventurer
Personally, I think purging the Realms of the powerful NPCs would actually hurt some of the charm of the setting. As a collection of maps and lore, I don't think the setting is all that special. The many conflicting personalities and the feel of the Realms as a living world is one of the things that drove it to high levels of success while other settings faltered.
I think the big thing to avoid is having the novels radically change the setting. The novels as part of canon aren't a bad thing, but players and DMs shouldn't be hamstrung by them. If WotC wants to put out a novel that pits Elminster against some uber big bad (say like Elminster in Hell, but with much less suck involved), that's fine. But don't have the consequences radically revise the whole world. That way, if DMs want to use elements of that story, they can, but they aren't forced to do so.
As to a massive retcon, the problem with hitting the reset button is that you're going to have some people vocally displeased no matter what. You can say "restart everything at the gray box," but that voids a lot of lore that was actually pretty good. The Time of Troubles, for example, was a horrendous event but brought out elements that many people like, including wild magic and the Baldur's Gate video games that many people like to work into canon in their Realms. That's also not to mention that just resetting everything to the gray box seems like a wate to me - if you want to play things like that, why not just get the gray box and say, "this is the point we're playing from"?
That said, the 4th edition Realms was unpopular enough that it's probably the one place I could see a retcon working from. It's not that the 4th edition Realms were bad, but they took gamers so far away from the people and places that defined the Realms that it might be a good idea to go back. Jumping the timeline 5 to 10 years ahead is one thing. Jumping it 100 years ahead and changing the basic physics of the world is another.
Overall, WotC seems to be setting the Sundering up as something akin to the New 52 in DC comics, where we're going to have elements from the past smashed into a post-Spellplague Realms. Maybe that will work well, but I get the bad feeling that it will probably be more confusing than any other option. Hopefully, that won't be the case and the Realms can go back to what made it such a strong setting in the first place.
QFT.
One of the charms of FR is it vast canvas of lore and depth added over the decades, me and my players have no problem with all the characters in the novels playing a role in the realms and in our games the exist and wonder around the world doing their own things, the realms is bg enough for both the characters and the NPCs to coexists without stepping on each other toes.
Warder