Mistake. Every muslim on earth would seek revenge.
Nuke Medina with the warning that Mecca is next.
Nope. Destroying Mecca destroys allah ... allah determines every thing down to the sub-atomic level and beyond. It cannot be destroyed, if that Islamic tenet is true, but if destroyed then it is a false god and Islam is over.
Many muslims said as much right after 911.
Payback for 911 is nuking Mecca during the haj with no warning. Nuking Medina is just to eradicate any remaining vestiges of Mohammad. Putting paid to the account, so to speak.