Why not a latter day version of A Comet (BOAC) failure? Some fault as yet unknown which brings about sudden absolute failure of the plane? Something in the timeline preclude this? Or is it unlikely as hell in the CAD/testing age?
A "suitcase" nuke, put aboard by the stolen-passport guys from Iran:
Detectable from U.S. satellites ? I don't know. It wouldn't have to be huge (megatons). < / speculation >