The Human Sacrifice of the innocent military officer, Wayne Jessup, to the monsters outside. And it's a totally pointless death that probably attracted more predators to the store, anyways.
Not everyone in the store was advocating for the sacrificial act, David for example tried to act against using Jessup as a sacrifice, but it was still sad, though the mob basically acted out of paranoid fear, and seemed to be under control of Mrs. Carmody. The fact though that everyone looked back at Mrs. Carmody, especially the first two guys who were smiling, comes off as very chilling, but the fact that everyone slowly turned around to look back at Mrs. Carmody, does seem a little perplexing of whether or not they were pleased with what they did.
Not to mention Jessup's death itself. After being stabbed and thrown outside he's screaming and repeatedly bangs on the door begging to be let back in only for them to lock him outside. Then he sees the giant monster slowly come up to him. Realizing he's done for, he backs up against the door and then tearfully pleads one more time to be let back in before he's ultimately killed.
There's something quietly sad about the collapse of Norton and David's relationship. While the two have had a tense history with lawsuits and property disputes, their interactions show them patching the bridge when the crisis initially seems mundane. Yet when David tries to explain the supernatural danger they're in, all Norton can hear is that David is betraying that initial trust to throw a childish prank. His own ego and refusal to face facts permanently breaks any potential reconciliation and potentially results in his death.
On top of Jessup's death there's also Ollie's. After being the most capable survivor, after saving Billy from the Pterodactyl-like monsters and after killing Mrs. Carmody, not only was he killed by the same monster that killed Jessup, he was the first person in David's group to reach the car and he was actually hopeful that they'll survive before dying a cruel, horrifying death.
The ending of the movie. Dear God, the ending. It's easily one of the, if not the most tragic, twisted, and downright sadistic movie ending EVER. Stranded with seemingly no hope of salvation, David mercy kills the four other survivors, including his own son to spare them the pain of being Eaten Alive by monsters. His mind broken from killing his friends and young son, David steps out of the car to face the monsters head-on, only for the military to arrive, meaning that if they had just waited a few minutes, they would've been saved.
is as upsetting as it is harrowing.