Mature content for me is a high degree of violence (the gory kind), depictions of sex*, sexualised nudity** and storylines dealing with heavy themes like rape and the survival thereof, incurable diseases like cancer, war, slavery, etc.
Of course, this all depends on how the author deals with it. There are children's books dealing with death and cancer and such, and One Piece - which is aimed towards teenagers - repeatedly deals with war, the loss of loved ones, slavery and the consequences of totalitarian government. So not all of the things I listed above necessarily add up to something being rated mature, but they're definitely things to consider - and certainly something that might be worth labeling individual pages as NSFW.
So yes, the delivery of said themes matters a LOT.
*) By "depictions of sex", I don't mean you can't IMPLY sex that happens off screen; I mean the showing of the actual act.
**) Non-sexual/casual nudity is fine with me, but this is very much a cultural thing, and any scenes with nudity should probably be labelled NSFW, or at least warned of ahead of time; some people might be reading these comics in places where sudden nudity, even non-sexual, may cause offense.