Check out Monster, by Naoki Urasawa.*
What can I say without giving away the plot? It's, uh, about a serial killer. And a doctor, accused of murder, who dedicates himself to tracking down the real murderer and killing the killer himself. About two mysterious kids. Neo-Nazis. Hospital politcs. Psychology. It goes on.
For those who aren't into manga, this really doesn't come across as manga. For one thing, the art reminds me more of Terry Moore, the creator of Strangers in Paradise, than anything else. The doctor's ex, it's like looking at a ghost. For another thing, there aren't seven million references you won't get, since the story's set in Germany rather than Japan. There are even a couple of western references that crack me up: the head of the investigation looks remarkably like a twisted version of Sherlock Holmes.
What makes it stand out? Great plot, very nearly four-dimensional characters, lots of tension. And moral quandries. Lots of moral quandires.
*(This means Dave.)