While some characters like Nadja and Colin are very over-the-top or Comically Missing the Point, Guillermo's more subtle reactions to Nandor going into Super Slumber are very sad, especially when he snaps at the camera crew to give him a minute while Trying Not to Cry. Thankfully, it doesn't last.
The death of Colin Robinson. The Wham Line at the halfway point of season 3 episode 9 suddenly and painfully contextualises an entire season's worth of uncharacteristically kind behavior from Laszlo, especially with Laszlo morosely admits there's not a thing they can do. For context, energy vampires die on their 100th birthday, which Laszlo knows but Colin doesn't: Laszlo decides to spend the season making Colin's final months happy. It's mitigated a little bit by the somewhat comedic nature of his actual death and subsequent rebirth into a creepy baby, but the Colin we knew is presumably gone for good.
The ending of the Season 3 finale, "The Portrait". Laszlo makes a unilateral decision to abandon Nadja so that he can take care of the reincarnated Colin Robinson, writing a touching letter explaining his actions. Guillermo and Nandor are affected by this as well, as Laszlo kidnapping the former results in the latter believing he was Stood Up on their planned world trip, as they both vainly cry out for each other, before Nandor defeatedly boards a train alone.
Season 4 often indicates that, as strange as he is, the Child Colin does feel normal anxieties every child experiences. He's notably disappointed when he can't find kids his own age to talk to and he confesses to Sean that he isn't entirely sure Laszlo likes him a lot of the time. Given his relation to the original Colin, it also demonstrates how energy vampires likely become so sociopathic when they don't get the luxury of a normal childhood.
Season 4, Episode 9: Guillermo, who has recently come out, invites his boyfriend over to New York. Nandor gets jealous and turns his wife into a clone of the boyfriend, driving a rift between him and Guillermo.
When Freddie goes back to England, Guillermo has to deal with Nandor and his Freddie clone getting close to each other, along with said clone crashing Guillermo's Skype sessions with the real Freddie. It really hammers in how toxic the poor guy's environment is.
Guillermo decides to surprise Freddie by coming to his homeland in England, only to find him kissing Marwa-Freddy in the distance. Poor guy can only blink back tears as he walks away.
In the season 4 finale, the death of Child Colin and rebirth of Colin Robinson. The cheerful boy Lazlo and Guillermo spent the season raising is effectively erased and replaced by Colin Robinson. Notably, Colin Robinson claims to have no memories of his year as a child, drains his victims through his usual tricks instead of his new aggravation tactics, and seems untouched by Lazlo's devastation of these facts. Meanwhile, it proves to be the final piece of evidence to Guillermo that nothing changes, pushing his decision to leave the house to find a new path to becoming a vampire. Laszlo's devastation is the single biggest gut punch the show has ever delivered; uncharacteristically, with more vulnerability he'd ever shown in the prior four seasons, he's all but begging Colin to remember the last year they'd spent together after Colin reincarnates.
Laszlo: You don't remember me bringing you up...from a...small baby?
Colin: No. Not at all.
Laszlo: Do you remember, um...me playing the piano, and you singing and dancing? And then sometimes we'd jump over the fence at the zoo in the middle of the night to look at the baby rhinos?
Colin: Yeah, no. Doesn't ring a single bell. Are you okay?
(Colin walks off down the hall. Laszlo slumps by the piano in pure devastation)
The credits of season 4 are accompanied by the main cast performing a melancholic take on "Sunrise, Sunset" from Fiddler on the Roof. Colin's verse ("I don't remember growing older") hits particularly hard with the added context, and the entire performance is done without the presence of Guillermo.
Adding onto the sadness of the whole affair is the fact that Laszlo, who had previously in the season taken great loathing to the idea that baby Colin was a fan of musical theatre (an artform he considers exceptionally low), can only fully express his heartbreak through a soulful and completely earnest rendition of one of the most famous musical theatre songs in the world.
In The Campaign Evie returns and Colin tries to tell her that he genuinely loves her but she can't reciprocate those feelings leaving Colin heartbroken.
Towards the end of “A Weekend at Morrigan Manor”, Nandor finally learns that Guillermo has been turned. He is utterly shocked and betrayed - a massive departure from his normally goofy demeanor - and had he not been in a cage at the moment, he would’ve ended his former familiar right then and there.
