I can’t find the original editorial in Kotaku that spurred this comic, but you can find the criticism in several places all over the net (like here and here). It wasn’t so much the killing that shook people up, but the fact that Drake was so charming and cavalier about it. Whatever. It’s healthy to ask the question “has the line been crossed yet?” from time to time, but in this instance I believe people are just uncomfortable with an idea of game realism that could cast light on the consequences of their actions (in this case, doing it by omission). Contra, Serious Sam, Uncharted: it’s always been just a game.
For a great commentary on the carnage that gamers engage without batting an eye, I recommend you give Metal Gear Solid 3: Snake Eater a spin. People who have played it can attest to the memorable river scene as something to think about. However, as with most thing Metal Gear, such exercises are better left as a brilliant postmodernist commentary on gaming: an exception, definitely not a rule.