The Word Weary/Analysis

Authority is inherently abusive.
John Kossler stated in the alt text of this comic that The Word Weary is NOT against government, but that the author distrusts people in authority because they will use their authority to "fuck him sideways." This comes up often in the narrative- and not just in the cartoonish villainy of The Mayor. Each of the characters (even many of the minor ones) is oppressed in some way or another: John is constantly tormented by Jason and Yorick, who are the dominant members of their group while Sam is suffering from sleep deprivation and is constantly abused by the customers at the restaurant he manages but is unable to quit because his boss can't promote a new person to his position. Stan Becks, the debt collector who lies to Elly forces her to pay back her mother's credit card is pressured by his supervisors to step up his collection efforts or face termination.

The main characters not based on John's friends are different aspects of John's personality.
This may belong in Wild Mass Guessing, but there may be enough evidence in the text that it's true. John has stated a number of times that Poor Trotmann is based on him when he's feeling down on himself and Grace's inability to take her job seriously even though "this job is the only thing keeping her sane" is an admitted reference to John's inconsistency in keeping the comic updated on time. Judging by his answer to the question "How much of The Word Weary is based on real life?" in his About section, the character John is thus less of an Author Avatar than how the author perceives himself. With this in mind we can make guesses into which characters are representations are parts of him: Grace seems to be the author's cynicism and his displeasure with his lot in life, Poor Trotmann his insecurity and The Mayor his distrust of authority. Elly may be a symbol for his ex-girlfriends as he said in the comments section of this comic that he found out a girl he was seeing was cheating on her boyfriend with him- just as Elly is doing with Harry. Lillith seems to be a much better match for him as she seems to be a nerd's wetdream. She herself plays Dungeons and Dragons, is ostensibly very attractive and is willing to settle for men she doesn't necessarily find attractive- but John pushes her into the arms of another man(specifically Sam), again showing the author's insecurity. Harry is most likely the author's cynical view of relationships personified. He lies to Elly and his sister calls him a "manipulative and deceptive creep," but they've been dating for a year.

Humans are weak.
In the comic John plays with the Humans Are Bastards trope. Most of the characters aren't motivated to do wrong by greed or maliciousness (except maybe The Mayor), but rather by their weakness. Harry lies to Elly so that she'll have to let him move in with her because he knows she's not ready to commit to him, Stan Becks ruins Elly out of fear of losing his job, Yorick uses Poor Trotmann to avoid feeling guilty about having to fire Branden and Jason has a drinking problem even though it's hurting his relationship with his girlfriend. John is willing to sleep with Elly even though he knows she has a girlfriend because of his loneliness and desperation.