The fundamental problem here is that the film is not true to it's own premise. The movie does not tell the same story, once as a comedy and once as a drama. Instead, it tells 2 different stories, whose only real similarity is that Radha Mitchell appears in both, playing a character named "Melinda."
Neither story is especially comedic -- save for one amusing scene involving Will Ferrell and a door jamb. Neither story is dramatic. You could say that the drama's attempt at tragedy is comically weak. That's as much genre analysis as the flick inspires.
What you have here is two short films, both only modestly compelling. That's a shame because the premise: that the only difference between comedy and drama, humor and pain, is perspective -- is an intriguing and true one.
It would have been quite an achievement to use dialogue, acting and exaggeration, to highlight the similarities between satire and sincerity. I would have loved seeing identical plots take different paths. Instead, we got two storylines on separate tracks, that converged only superficially.
Neither story plumbs the characters or their relationships deeply enough to unearth any discoveries about human nature. Infidelity is a theme, but it means little, impacting the plot but not the people. Adultery doesn't hurt. It doesn't anger. It just exists. At one point, Will Ferrell's Hobie declares that he's in love with Melinda, but we don't know her well enough to understand why he would be. She showed up at his apartment one night fresh from a drug overdose. She stayed for his party and if anything moving happened between her suicide attempt and his hor dourves, it happened off screen.
The tale of two Melindas shortchanges each of them. We switch back from one story, just in time to prevent the other from achieving any substance. If the device of showing comedy and tragedy as sides of the same coin had succeeded, then maybe the story itself would not have mattered. But once that experiment failed, its remaining components were insufficient to sustain a movie, let alone two of them.