Completely useless (and cannot be launched) if the target (or the territory of all enemy nations) is protected by a Missile Shield. Coupled with the above, Nuclear ICBMs can become an annoyance, as they cannot be destroyed unless the silo is razed.
If an enemy launches a nuclear missile on a city, they will mainly launch on a key city. An ideal strategy would be to spread out your buildings so that not all of them can be struck, especially if the city has a wonder.
Don't fire Nuclear ICBMs until you can build the Space Program. The Space Program eliminates the effects of a Nuclear Embargo. You can also see the entire map, so if an army is preparing to strike a city, they can be sighted and eliminated.