This is just wishful thinking on my part probably, but it would be nice if every skill/rune combo is never "useless." For example, horrify has zero effect on King Leoric. I get that he won't run in fear, but it would be nice if it did something, like minus to armor, damage, or resistances. Blinding flash is an example of a skill that does it right. Elites aren't blinded, but they do have an increased chance to miss. I don't think there would be that many skills that would need some tweaking.

If there are skills that do have no effect at all on certain bosses, then the skills still should be useful in that encounter. Because Leoric summons skeletons, horrify does have a use for that battle, but I would imagine there are some battles where horrify, and skills like it would have no use because there won't be other minions.

This might not be worth trying to do before launch, but I think it would be worthwhile to look at for a future patch.