(ignoring magic missile or specific powers, and back to the OP's original question)
visual signs are not the only way you target something. you also have your other senses (hearing, smell, etc).
There are sounds of combat, shifts in air, the smell of an unwashed carrior crawler. that is part of why you don't need line of sight (only line of effect), because you have other senses to tell you where someone/something is.
You also have allies who might also be giving you guidance as to where something is (maybe you hear them fighting something, maybe they flat out yell and tell you "X yards at 11 o'clock ..." etc.) but a battlefield is far from silent or odorless.
Even from other PCs even if the players aren't actually saying anything, there are surely some shouts of pain or clang of sword on armor, etc.
So, basically, even without sight, you have other senses that help you target.