I believe the Guided Missile should simply be a capability for naval units. Using one would expend like 20% of your ship's health (since health represents its state of supply and combat readiness as much as how much damage it has suffered). As it is, if my sub encounters an enemy cruiser, it can't sink it. But if it launches a missile or two at it, the cruiser gets no defense, and is now weak enough that my sub can sink it. Additionally, cruisers used as missile platforms would not be as capable of defending stacks - this is realistic, since cruisers rely on missiles to do their jobs, and if they're out, they can't do their jobs, now can they? Of course, this doesn't do anything about the no-defense-against-missiles thing, but that can also be fixed with another alteration.
All that aside,
Missiles are not a universal use-this weapon. It has a few specific purposes, and trying to use it for other things will be a waste, just like trying to protect a stack of catapults on a hill with a horse archer.
They are best used when launched from ships, which means coastal cities and stacks are their targets. Unlike airplanes, SAMs and orbiting jet fighters won't do anything about them, so you can tag that tough defending unit and make the enemy city/stack easy to kill. They can also be quite effective in blunting enemy attacks - their short range isn't important when the enemy is marching toward your city, and again, they don't get to defend against them. And they're fairly cheap, so those low-production cities you have can be cranking them out. They're also easily relocatable to any friendly city or fort, so getting your ships restocked isn't that hard.
And I already went over the strategy of using them to soften up tough units.