Quinn becomes a believer in guardian angels after watching a television special about them, and although Daria remains skeptical, she's unable to convince Quinn after a series of events seems to validate Quinn's beliefs.
After watching a television show proclaiming the existence of guardian angels, Quinn finds religion and believes that guardian angels are monitoring even the minor details of her life. Daria is, of course, skeptical (and annoyed), but that's not the least of her problems: Jane is pressuring her to go to a party that's being held in Brittany's honor to celebrate her "C-" average (a party at which Mystik Spiral is performing). Jane finally convinces her to go by reminding her that Quinn would be mortified if they went.
Quinn's new-found spirituality is reinforced when she narrowly avoids being hit by a falling light fixture that Jake is attempting to install, claiming that her guardian angel saved her. Stacy and Tiffany are also convinced, as are the Three Js, but Sandi doesn't buy it. However, there's no stopping Quinn, especially after the rest of the Fashion Club becomes ill after eating salad with bad dressing from the school cafeteria. Daria becomes increasingly irritated by what she sees as her sister's faux spirituality and obvious gullibility, an attitude that starts to irritate an exasperated Helen, who sees nothing wrong with what she sees as an essentially harmless belief.
At Brittany's party, Sandi takes every opportunity to gloat when Quinn is twice humiliated: once when Brittany's out-of-control brother Brian soaks her with a drink, and again when she leans on Mystik Spiral's mixing board, causing electronic feedback that shatters the gift that Brittany's father bought for her. At home, Quinn is mortified at what she believes is the loss of her guardian angel; Daria is sarcastic at first, but relents when Quinn turns to her for advice, asking what she believes in. Daria's unsarcastic answer "Quinn, until I see some pretty convincing evidence to the contrary, I think we're on our own."
When Quinn finds that "so sad", Daria hurriedly adds that she doesn't have proof there isn't something in order to keep her sister happy and supports Quinn's beliefs. "I think what makes sense is to believe whatever makes you feel best", she tells her. Helen, who's been listening, tells Daria she's proud of how she set aside her own strong beliefs to comfort her sister; Daria denies that she was doing this and gets a sarcastic response of "whatever makes you feel best"...
- Jane tells Daria that the real reason she's bothered is because she's worried that it's true: there are higher powers looking out for people like Quinn and that's why they fit in so well, and everything is rigged against people like them. It's not known if Daria is actually worried about this but Jane seems to be, since she's left depressed after saying it.
- The website Reburb states that performing at Brittany's "really ruined their [Spiral's] credibility for a while. There were pigs in a blanket, though, so it wasn't a total washout."
- Helen claims that she's spiritual.
- Steve Taylor "borrows" money from his son's college fund to pay for gifts for Brittany.
- Mr O'Neill goes to Brittany's birthday party. That's quite weird.
- Stacy implies she once peed herself in public, saying an "accident" is "so humiliating you just want to die! ...um, I imagine."
- Ironically, "It's a Miserable Life" makes it canon that guardian angels do exist and so does God: this means Quinn is right and Daria is unknowingly wrong. This, of course, was not the intended moral of the episode.