DALE: Steps in missile defense

The nature of the threat (massive preemptive nuclear missile launches) has changed. The current threat, which is only going to become more severe as countries like Iran perfect offensive missile delivery platforms, is defending against a single long-range nuclear or biological missile, aimed at a major western city, launched from anywhere at any time. How do you run a sane cost-benefit analysis of a defensive system cost against the destruction of Paris, or London, or NYC...?