It's an interesting idea. And you just know there's going to be a 'but...' after that 
But
I think it would change certain missions into another kind of game, not necessarily a bad one, but a different game nonetheless.
Bad guys can attack civilians - so why don't they just kill the hostage you've been sent in to save the minute you enter the mission?
Unless the civilians are super-resistant (they're already more resistant than your average defender or petless Mastermind), they'll be downed by a Boss quicker than you can fire two holds on them to stop it from happening. So there would need to be a change there to make the civilian stronger than a Tank, which for me breaks the immersion.
My alternative would be to have special content that measures 'collateral damage'. Kind of the same as the TF/SF/Trial MO requirements. It also makes this kind of 'gently, gently' approach to being a superhero/villain optional for those who really just want to obliterate everything in their path (miraculously avoiding hitting the civilian they're meant to rescue/kidnap) rather than make sure the building doesn't collapse before everyone's out.
Remember, there is a built-in pause before the initial alpha. I call it the "Dramatic Pose" moment and in that moment there aggro shifts to you. The "Hit-the-Deck" command would add a -aggro check to the NPCs.
"Samual_Tow - Be disappointed all you want, people. You just don't appreciate the miracles that are taking place here."
Yes, this is a thread promoting killing/defeating civilians and before the obligatory "...but this game is rated T for teens", remember Call of Duty has the same rating. The idea add a new dynamic to the current game-play by motivating players to actively protect NPCs because they can now be attacked by the enemy. To do this, we would have the ability to buff NPCs and give them basic commands like "Stay-Close" or "Hit-the-Deck" to prevent them from drawing needless aggro. The narrative works for villains who are doing the kidnapping as well since they are more valuable alive than dead. In the case of Bank missions, where villains can attack NPCs, you would be able to incapacitate large groups of NPCs to a sliver of health at which point they will be laid out, but alive, and will not be target-able anymore.
XP can be given for either protecting or incapacitating NPCs respectively as well as badges and recognition. As a Rogue or Vigilante NPCs will con yellow, so you can chose to help or hurt them, ie. attacking a mugger = Helping, attacking the mugger AND the victim and robbing them yourself = hurting. These will eventually go toward changing your affiliation to either good or evil. Overall, the emphasis will still be on "incapacitating" civilians in the same vane as "defeating" or enemies.
"Samual_Tow - Be disappointed all you want, people. You just don't appreciate the miracles that are taking place here."