Spoilers.... Since this isn't a comedy, the funny lines are window dressing. There are plenty of them, and plenty of them are memorable, but the best line is the one that perfectly defines Ryan when he shows up at Alex's door in Chicago. As he's backing away, and she's closing the door her husband asks who was at the door. She replies, "Just somebody who's lost." We don't even see her as she delivers the line. It's treated as a throw-away, but it's the heart of the film.
I admire this and other Jason Reitman films I've seen because they confront real human problems with wisdom and compassion. It's a relief that Hollywood can still produce movies like this when the public interest is so fixed on situational ethics and violence. There's immorality in Reitman's films, but it's always measured against a moral scale. This movie spends a great deal of time establishing the glamor of Ryan's life, transitions to a more equivocal view of his rudderless and goalless existence, and ends with his standing motionless, looking at a long list of destinations. Alex's line captures him perfectly.
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