A first strike requires reliably hitting a bunch of targets, often on a schedule. If your intended target has a possibility of randomly (from your viewpoint) taking out some fraction of these incoming warheads, how much more complicated does that make your plan?

If you're talking about protecting a target (nation) from an attack, then "Missile Defense" shouldn't even be your first line of defense. Civil Defense is to protect the people's lives, anti-missile defenses to protect their possessions and those who don't make it to a shelter in time.