If it's necessary for the story, out they go, plain and simple. If it's too easy to kill them off, then I must assume they weren't that great or important of a character anyway. If it takes a lot of effort, or is an emotional moment for me, then I feel confident both that I did the right thing, and that they were a character that evoked a lot of emotion for me.
So far, nothing terribly interesting on the killing-off front. Mostly it's been more interesting what I've done with them post-death.