Don't kill Elminster - that's overdone.

Instead, kill Khelben, Laeral, and ALL of the NPC's in Waterdeep (Large meteor strikes JUST west of Waterdeep, massive tsunami WIPES THE CITY CLEAN, as well as Baldur's Gate and any city within a hundred miles of the Sword coast).
In an event that big, there are certainly repercussions. The priests of Eldath, Akadi, Selune, and Chauntea would all fall down screaming, as the voice of their goddeses crying out in pain over the massive destruction and altering of the environment, as well as loss of some of their greatest temples (in the case of Selune). Priests of Umberlee would get an unsettling feeling, as if they had just seen their mothers get beaten in front of them. Priests of Kossuth would feel a sudden rush of Power, and priests of Grumbar and Chauntea would feel punched in the gut; etc. etc. Mages with teleport gates on the sword coast would notice massive backlashes in magic on their gates. The sky would be lit with fire and then a massive mist for miles east of the Sword Coast, as well as the minor earthquake felt as far as the Dalelands, and and sudden west to east waves in the Sea of Fallen Stars. The Roads to Icewind Dale would be destroyed, causing massive trade problems, etc.
Have Elminster finally slip into madness, as people have been hinting all these years. The remaining Major NPC's (Alustriel, Symbul, etc.) have their hands full trying to clean up not only the disaster, but all the unfinished business that these worthies have left behind.
Then, have a disaster (Evil Adventurer-hunting squad) start picking off all those second string NPC's that the Big Boys would turn to. If you are an active adventurer, word on the "street" is you are getting snuffed by a squad of 50 mid to high level Drow / Githyanki / Slaadi / whatever.
THEN turn the real plot loose and tell the PC's through Alustriel or whomever "you're on your own."
