It's all software.
At their apogee, missiles don't have any thrusters, they can't turn. Adding maneuvering thrusters to a MIRV would be infeasible to do quickly, since you are essentially designing a new spacecraft.
That means you won't be making any significant hardware changes to the missile and warheads. You can get-r-done in software, except for fuzing, but bombs having multiple interchangeable fuzes (detonators) is almost as old as bombs.
The whole rest of this answer is about fuzing,
Mostly nukes are fuzed for altitude, though impact fuses are an existing (though fairly evil) option. You won't get the chance to develop a RADAR style proximity detonator for a MIRV. They don't already have them, and up til now there'd never been a use for one, unless they happened to use a RADAR altimeter you could hack for the purpose. (I am not an expt on nuke fuzing methods, nor should I be.) Anyway you'l need a ton of them, so it needs to be something you can quickly implement.
A starship will be just like any other point defense: its point defenses will have limits. If you heard the phrase "Interceptors are running hot" on Babylon 5, that is a warning that the enemy fire is coming faster than the interceptors can defeat it, and the ship will start taking hits.
Stalin said, "quantity has a quality all its own": a Soviet hallmark, not to mention an American one in WWII on both fronts. So it is right out of the playbook of both large nuclear powers: this swarm philosophy is why they are large.
Presumably an advanced translight enemy has heard of both A-bombs and orbital missiles. It can shoot down our missiles all day. You're betting the planet that they can't shoot down 500 in 5 seconds. All this to say, this "time on target" approach will require an awful lot of fuzes.
Another reason for a swarm is to shotgun, much like the Hedgehog in WWII, so maneuvering is not effective.
The bigger problem is the ones that miss
Ok, so you got him. Unfortunately, the ship's bits pelted the west Atlantic. That's not the unfortunate part. It's that his position when hit was over the ocean west of France. That's not it either, the unfortunate part is that 460 missed shots launched from the Dakotas pelted the Holy Lands ranging from the Dead Sea to Pakistan, including wild shots that landed in Macedonia (both), the Donbass, and an Ulster's farm field. No harm done, they were fuzed to not detonate if they missed the ship.
Oh wait. Have you read Tom Clancy's The Sum Of All Fears?
At this point, you might as well take a shovel to every major city. Because it's no longer a question of "if", but "when". Thanks, aliens.
So you see where fuzing is a big deal, and there really aren't any good answers.
- Detonating near the ground is out of the question, obviously.
- If you fuze to detonate them in space or high atmosphere, you get massive EMP that does damage to satellites and on the ground both. France would be knocked back to the stone age in a flash.
- I can't see a technical way to get the MIRVs to sabotage themselves as reentry vehicles, e.g. Deliberately enter facing backwards and burn up in atmo, not that a huge injection of plutonium into the sky would be particularly awesome either.
- Really your best bet out of a lot of unpleasant choices is to let them land with a thud, and take your chances with finding them all before another of Clancy's books turns real.