I don't really feel sad when I kill NPC's in games, and for the following reasons. 1) whenever they are attacking me, it becomes a situation of survival on my part, which takes away te guilt from their kill, 2) since enemies and NPC's are often repeated, the shock of killing one is taken away when I kill 50 other clones of that NPC, and 3) in games like MW2 where there are other forces that are killing NPC's, me killing the NPC's is more an act of trying to speed up the progress rather than perfroming acts of cold-blooded murder.
There are however a few exceptions to this:
1) the colossai from Shadow of the Colossus. As well as only really attacking because I am posing a threat to them rather than the other way around (# 13 doesn't even attack you, he just tries to escape you), the ending of the game really strikes the idea in me that all those deaths not only got me nowhere in terms of my end goal, but also created a situation where countless lives are now threatened and lost (if Mono is indeed the Queen in Ico), all because of my selfish wants.
2) any dog (except wolves, cerberus, or the dogs from Demons Souls) because, well, I just love dogs and hate to see it when I'm the one killing them.
3) the enemies from Condemned 1. This may seem like a strange answer, but besides the manniquens and those of The Oro, the rest of the enemies are either those being manipulated by the Hub-caps late explained in Condemned 2 or simply those who have become the victims of an uncaring society, and while enemies are repeated, that aspect is negated when 1) you rarely ever see what the enemy looks like till they die and stay still, meaning the enemy can really be anything, making their death that more meaningful, and 2) even if they are repeated, the way each enemy looks further drives in the point that these were victims of an uncaring society who, becuse of their mistreatment, were doomed to end up like this.