Lois falls into this in "And I'm Joyce Kinney". While the titular character is the main antagonist of the episode, many fans do not see Lois in the sympathetic light she was intended to be portrayed in, due to her behavior in post-cancellation seasons. Had this occurred in earlier seasons when Lois was more likable, Lois probably would have been more sympathetic. The schoolgirl prank Lois pulled on Joyce when they were younger also caused her to be seen as an Alpha Bitch.
In "Roasted Guy", the viewer is meant to sympathize with Peter after his friends throw him a roast and accidentally hurt his feelings. However, Peter had specifically requested that his friends "Leave no punches", making him look immature and thin-skinned when he turns his back on his pals and tries to replace them by befriending three women.
"Quagmire's Mom" gives Quagmire a sympathetic backstory to explain his deviant tendencies: His father is a celebrated war veteran who set up unrealistic expectations as to what masculinity is, while his mother is as much of a sexual deviant as he is now, skewing how he views relationships. And when Quagmire is prosecuted for sleeping with a 15-year-old girl who claimed to be an adult, he is portrayed as an innocent victim of a flawed legal system. In addition, the only two women Quagmire truly loved (Lois and Cheryl Tiegs) both left him, causing him to try and fill the void by having meaningless sex with countless women. The fact remains, however, that Quagmire is a repulsive sexual predator who knowingly and gleefully shares his numerous sexually-transmitted diseases with the women he sleeps with (lying about wearing protection if he needs to), making him extremely unsympathetic to the audience despite how many times the show tries to give him sympathetic episodes (him trying to help his sister who's in an abusive relationship, him being tricked into marrying a prostitute, him being trapped in an abusive relationship with a "female Quagmire", etc.) In fact, "Quagmire's Mom" outright had Brian (whom Quagmire absolutely and hypocritically loathes) states he's a grown man who should own up to his behavior instead of using his mom as a scapegoat. In response, Quagmire tries to take the high road by asking why a known atheist like Brian is defending his now religious mother despite that Brian's statement had nothing to do with defending Quagmire's mother.
Throughout the entirety of the show, Quagmire has treated women like objects and raped far too many of them to count. In this episode, the viewer is supposed to be touched when he tells his sister that women are "strong, vibrant and beautiful creatures", but his past actions make him look hypocritical at best and manipulative at worst, and when he tells Brenda she doesn't deserve to be called a woman, he only comes across as a prick.
Joe's strong commitment to the law is showcased when he explains that he can't arrest Jeff unless Brenda files a report, as well as when he threatens to arrest Quagmire himself when the latter comes up with a plan to murder Jeff. However, Joe had personally witnessed Jeff's abuse many times and never did anything to prevent it from happening, making him look incompetent and uncaring.
In "Peter-assment", Peter's boss Angela starts sexually harassing him. She later tries to rape him, but when he runs away, she tries to kill herself because she hasn't had sex in 10 years. The episode plays her suicide attempt and longing for affection as tragic, despite her disturbing behavior early on.
"Bri Da": Quagmire becomes jealous that Brian is dating his transgender father Ida. While Brian is rather condescending towards Quagmire, he at least tries to bond with Quagmire and generally loves and cares about Ida, genuinely wanting a relationship with another woman (compare that to how most of his previous conquests were shallow, moronic bimbos who he only dated so he could lord his intelligence over them), and Quagmire forcing Ida to end the relationship after he forces her to choose between him and Brian makes him look like a spoiled baby.
In general, any attempts to make the members of the Griffin family sympathetic in later episodes of the show don’t work due to all of the heinous actions they have committed over the course of the series. Examples include trying to have a Freudian Excuse for Peter's treatment of Meg in the episode "Peter's Sister", where it is established that he has a Big Sister Bully who heavily resembles Meg. Despite how awful his sister treats him, many find it impossible to sympathize with him after the things he has done throughout the series, such as throwing a heavily injured Stewie under the car to be run over. Other examples include trying to have episodes that show Brian in a sympathetic light after the episode that had him infect Chris and Stewie with Herpes for no reason at all, despite knowing Stewie is the reason he's still alive.
