The opening sequence is itself terribly sad: Ellen, a profoundly lonely girl, prays desperately for any sort of comfort and companionship to ease her solitude. Unaware of her psychic abilities, she unwittingly finds herself in the sights of Count Orlok, who will prey on and violate Ellen both mentally and physically for the rest of her short life. She was was simply looking for a friend, and instead received a predator.
It's clear that since childhood Ellen has felt like her otherworldly, supernaturally-attuned nature means something is wrong with her, putting her outside the reach of most people, and even the friends she does have struggle to understand this side of her. Professor von Franz is a dusty old eccentric who's devoted his life to magic and the occult, but he has much respect for both her witchy qualities and her essential goodness. After the two of them gravely discuss what must be done to put down Orlok, von Franz tells Ellen quite wistfully how in another time her qualities would have made her a great and revered priestess of Isis.
After Thomas (accidentally) signs Ellen away to Orlok, the Count abandons the confused man by the fireplace for the night which, by itself, is eerie. The tragedy comes in when Thomas helplessly cries out that Orlok still has the locket with a picture of his wife in it, yet the man is powerless to take it from the vampire. Nicholas Hoult's heartbreaking delivery sells it.
After their respective ordeals, even sharing a bed is hard for Thomas and Ellen. Ellen holds her newly-recovered husband close, but he panics and feverishly cries for her to get away from him. Ellen understands, but is clearly heartbroken and hurt.
The deaths of the Hardings. The entire family is systematically killed with absolutely revolting cruelty. Orlok first places Friedrich in a deep sleep so he won't even know what's happening before brutally attacking his and Anna's two little girls, waiting until a panicked Anna rushes in to help them before finishing them off so she can watch them die before he kills her too. Friedrich is spared immediate death, but not out of mercy - rather, Orlok infects him with plague so he can die the next day in the full knowledge that he failed to protect his family. Understandably, Friedrich is so crushed he basically loses his mind. On his last day alive, he's a hollow shell of a person and goes to the casket of his dead wife, reminiscing about good times before opening it. Ultimately, he tragically dies of the plague next to his dead wife.
The ending manages to be more tragic than even 1922. Ellen sacrifices her life to stop Orlok and let him die in sunlight. But Thomas learns that his wife planned to sacrifice her life, and von Franz knowingly allowed it. He runs home in horrible apprehension while the sun rises and can only close Ellen's eyes in her deathbed. He loved her utterly and is left grieving the love of his life while von Franz can only honor her sacrifice and gently ask Thomas to forgive them. Perhaps even worse is him finding Orlok's corpse, naked in bed with Ellen and the horrible knowledge of how deep her sacrifice went.
In the span of just 3 days, Thomas has lost everyone he's held dear: His best friend, his friend's wife and their little girls and unborn son, and the only woman he ever loved. Thomas is now like Ellen at the beginning, completely and utterly alone in the world. In the long run, Thomas will most likely cross the Despair Event Horizon due to everything that's happened.
