In the first episode, when Five falls through the portal and returns to his family, Klaus asks, Does anyone else see a little Number Five, or is that just me?" On first watch, one might not think anything of it, until you remember Klaus can see the dead. He's genuinely asking if the others can see Five, because if they can't, it means Five would have died shortly after he disappeared.
Why is Ben's hood covering his face for the first episode? Because Klaus is still stoned, which impedes his powers. Ben's hood moves further back as Klaus has to stop binging, and finally we can see his face when Klaus's level of drug/alcohol use goes lower and lower. The topper is him actually being able to physically affect things when Klaus is totally sober.
It makes sense that the others wouldn't believe Klaus when he said that he was able to contact Ben and Reginald in the afterlife since he's been on drugs for years to inhibit his abilities, hasn't successfully used his powers since he came back to the academy, and is generally messing around with them instead of being helpful. After all, who would believe that just two days of being off of drugs that you've been taking for years would suddenly let your powers be useful again?
How can the viewers figure out that Vanya might have a part to play in the apocalypse? When Five jumped to the future, he saw his siblings dead beneath the rubble of the academy, but Vanya wasn't amongst any of them.
Of course, the fact that the first episode establishes that she lives in an apartment nearby and lacks powers, justifying her presumed absence during the final confrontation works as a means to decoy viewers from noticing this on the first viewing.
The great irony of "The Day that Wasn't" is that, had that timeline not been retconned by Five time-traveling to the morning, the siblings would have all been in a better headspace to confront their situations and possibly stop the end of the world. Vanya finds out that Reginald knew about her powers and had them suppressed when Allison isn't around for her to attack. Because Luther's off with Allison, he doesn't lock Vanya in a cell because she doesn't attack Allison. In addition, Klaus sobers up enough to contact Dave, and Grace is about to confess one of Reginald's secrets to Diego in a peaceful moment.
Why do simple prescription antidepressants work to counter Vanya's powers? They're still drugs. As long as she's taking them, she's not properly sober. Assuming that everybody's powers work similarly to Klaus', which wouldn't be too big a stretch, considering they all got said powers from the same origin.
If this is the case, then it adds a new dimension to Klaus' urgency when trying to find Luther and bring him home: He knows that if Luther is high, his super strength won't work properly and Luther won't be able to defend himself.
A very brief glimpse of the notes Reginald kept states that Vanya needed to be kept "sedated". Since her powers are connected to her emotional state, sedation would keep her from having strong feelings (which you can see in her behavior before she goes off of them).
When Five retcons Wednesday's events out of existence and starts the day over, why do Hazel and Cha-Cha still receive orders to kill each other, if Five is no longer at Commission headquarters? Because the headquarters are located in 1955. Everything he did during that day can't be retconned by a jump back to Wednesday morning, because in 2019, they're in the past.
If Klaus was so horrified by the sight of Vanya locked in the soundproofed room, why didn't he try harder to let her out? Pay attention to the look on his face in the scene following, where he's trying to play pat-a-cake with Ben and make him corporeal. That look of determination makes it clear he's going to head back down to the basement and give freeing Vanya another try once he has backup.
Ultimately, both The Academy and The Commission suffer serious setbacks due to their failure to recognize signs that members were seriously disaffected, and more importantly failing to properly address it. This sort of thing is a pretty common source of problems for Real Life organizations.
How is Allison able to get the drop on Vanya Hargreeves during the climax? Vanya's powers are focused around her sense of hearing, and she previously muted Allison. She couldn't hear her sister approaching while playing her violin, and Allison approached her from behind while she was focused on her other siblings in front of her.
On the subject of Allison's powers, with her powers, Allison was the most poorly equipped to threaten Vanya, since Vanya's powers are sound-based like hers, but Allison's powers require her to give a preemptive announcement. There was pretty much no other possible outcome to trying to Rumor her.
The Handler mocks Hazel by saying she thought he was the smart one when he decides to turn on her in the end. Hazel's intelligence is actually the cause of a lot of problems for The Handler, since it causes him to second-guess his actions early on and not give the Handler or Cha Cha a chance to fight back in the end. The Handler is dead before she has a chance to finish monologuing.
Luther and Vanya are both Not So Different in at least one aspect: Their father effectively subjected them both to Solitary Confinement. Where Vanya was locked in a sound-proofed cell, Luther was sent to the moon for four years. For all intents and purposes, a space capsule surrounded by vacuum is a sound-proof chamber with no hope for visitors. And while Vanya was locked in there ostensibly for everyone's protection, it seems that Luther was sent to the moon purely so Reginald wouldn't have to deal with him.
Although he frequently gets the Ron the Death Eater treatment for this, Luthers decision to lock Vanya in the soundproofed room is probably what enabled her to survive in this timeline. In the one where Five got stuck, it appears she ambushed her siblings and killed them before generating enough energy to burn herself alive and end the world. In this timeline, however, her siblings are all fully aware of her powers and the threat she presents when she escapes, and are able to escape the Academy before she destroys it. Because of this, Allison is able to cut her rampage short before it kills her and everyone else. The world still ends, but Vanya doesnt die in the apocalypse she created.
Vanya found little success as a violinist not necessarily because of a lack of talent. Her medication was meant to dampen her emotions which would have an effect on her playing. She might be technically proficient but with a very flat emotional landscape, Vanya would have had a hard time summoning that creative spark that marks true mastery of an art form.
The baby in the prologue is heavily implied to be Vanya, not only because of the Russian name (albeit a boy name) but in the scene where Hargreeves came to buy the baby, the lights are flickering violently in line with Vanyas powers.
Vanyas powers is again foreshadowed in episode 1 during Luther and Diegos brawl at Hargreeves funeral: Vanya shouted No! after Diego threw his knife at Luther and the knife only grazed Luthers arm which visibly surprised Diego. Vanya unconsciously interfered with Diegos planned trajectory for the knife.
The scene in episode 9 where Vanya is locked in a soundproof bunker is already heartbreaking, but Klaus' horrified expression and his insistence on letting her go adds a whole new layer of awful to the situation when you realize that he probably understands exactly what she's going through and is being reminded of his own childhood trauma of being locked in the mausoleum for hours.
Diego being afraid of needles could be from when Reginald forced him and his siblings to get tattoos. As a child, Diego was the one trying his hardest to seem strong while getting his tattoo, but the experience likely traumatized him.
So many of Klaus' lines sound funny at first and then depressing upon closer inspection.
"The longest I've been with someone was, I don't know, three weeks. And that's only because I was so tired of looking for a place to sleep" paints a very harsh image of what his life has been like the past years, but its casual delivery paired with the scene's abrupt and comedic ending make it sound a lot lighter than it is.
Another particularly worrisome line he gives is mentioning that he doesn't remember his first time. He could have meant that it was nothing special to him and he just doesn't remember which of his escapades was his first or, horrifyingly, that he was not in a state of mind to consent to it happening.
We get so used to seeing Number 5 as a grown man trapped in a child's body that it's easy to forget he was actually thirteen when he became stuck in a post apocalyptic world completely alone. If that's not bad enough for you, then there's also the fact that he was also thirteen when he came across the dead bodies of four of his siblings lying under the remainder of his home.
Another reason why Vanya was terrified over accidentally slicing Allison's throat? She took away her ability to speak, and the use of her powers.
The scene in which Five is found drunk at the library might seem funny at first; then it's revealed that Five was actually living in the ruins of the library during the post-apocalyptic future. Taking into the account that he only seems to use his room at the academy as a temporary base of operations, the library might very well be the only place Five can feel safe...
Reginald has Vanya's cell upgraded between her stay when she was five and her confinement now. He's completely soundproofed the room so that she can't harness sound to boost her power. The longer Vanya stays, the more she breaks down. The silence of anechoic chambers makes people freak out.note In the world's quietest anechoic chamber, the record for any person staying in there is 45 minutes In the dead silence of the room, a person's ears adjust and can hear the body's internal organs functioning. At the apex of Vanya's torment, the sound of her heartbeat is very loud; that's the sound she harnessed to blow the doors off.
The scene where Diego shuts Grace down is heartbreaking enough before you remember he's a vigilante who jumps on 911 calls to try and save innocents by any means necessary. When we first see him do this, he's successful and the family escapes safelybut there had to have been some instances where the bad guys won and good people died. How many times has Diego looked into the eyes of a dying victim and said "It's gonna be okay"?
When Klaus confronts Reginald, he mentions being locked in a mausoleum when he was 13. The actor for that flashback, though, is credited as Klaus, age 8. This could be a continuity error...or it could be the result of Reginald gaslighting Klaus into believing the first mausoleum incident happened when he was much older than he actually was.
Alternatively, it could imply that Reginald did this to him more than once.
In the montage about Vanya's book, we see Five reading it in the future. While the montage is pretty funny, there's also the fact that Five vanished when he was thirteen. That means this book—which describes the siblings as "never a real family" and made Diego so angry that he says Vanya shouldn't even be at the funeral—was his last connection to his siblings. He doesn't seem to have taken it personally, but it's not exactly a happy family narrative to guide an isolated teenager through growing up in the postapocalypse. Also, since Ben was still alive when he left, but dies sometime before the main action is set, Five would not have found his body in the rubble, so 1) he might have been holding out hope for Ben's survival, 2) the book is probably how he found out Ben died.
Although Luther's time on the Moon has become a running joke among fans, some easy-to-miss details paint a much darker picture. One of the packets Luther sent down, for instance, bears the words "REMINDER: PLEASE SEND MORE FOOD" on the label, implying Reginald had not been the most diligent about providing for his son's basic needs despite knowing Luther was entirely dependent on him. And since solitary confinement can have devastating effects on the psyche, the fact he spent four years with very little human contact places his aloofness and aggression toward his siblings in a far more tragic context.