“Would the Jews pack it in if Jerusalem was nuked? Would Catholics give up is the Vatican was destroyed?”
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Nuking Mecca would wipe out 2 of the 5 pillars of Islam - the Salat (daily prayers to Mecca) and the Hajj (pilgrimage to Mecca).
There is no Christian or Jewish equivalent for Vatican City or Jerusalem.
This would put a serious dent in a third pillar - the Shahadah. Hard to claim no other God except Allah when the infidels have wiped Mecca from the face of the earth.
And if you think that wouldn't make them fight harder and hate more then you're just kidding yourself.