- The descent onto Tau Volantis is a noteworthy moment, especially in cooperative.
- The drill sequence. Dismembering Necromorphs while a giant rotating drill destroys everything around you.
- The Reveal after reassembling Rosetta. In a series that's only ever shown hints and remnants of alien life, you suddenly learn the origins of the Markers and the ancient alien species connected to them. A mindblowing revelation, In-Universe and out.
- After Ellie is killed by Danik's intervention, Isaac finally loses his cool. While he isn't screaming incoherently, he outright states that his only goal is to take down everyone and everything responsible for the necromorph plague... even if it kills him. The entire next chapter consists of one long rampage through Unitologists and necromorphs alike, as you pursue Danik into the bowels of the earth. A full swarm of necromorphs, an entire company of Unitologist troops, and even the hulking new alien necromorphs fail to stop you, all culminating in a vertical chase sequence where you battle all the aforementioned threats while rappelling into an abyss. According to the Unitologist radio chatter, they're more afraid of YOU than the undead horrors pouring out of the woodwork!
Danik: Where is everyone!?Unitologist Soldier: All dead! Isaac Clarke... he shot the rest!
Isaac: [with so much venom that Carver steps back] Then we're gonna make sure he never gets there.
- It's also worth mentioning that for most of the series, Isaac has only been fighting in self defense. This time, he's launching a one (or two) man assault on the people and monsters that have made his life a living hell.
- After he and Carver escape the gas, Isaac is initially teetering on the Despair Event Horizon, until they get to the elevator. Then he switches to Tranquil Fury with almost disturbing speed. Carver points out that Danik is still going for the Machine.
- Isaac's Eleventh Hour Superpower near the end, activated by stepping on marked plates on the ground. It powers his Kinesis and Stasis, to the point where he can rip off limbs from still-alive Necromorphs and slow them to a literal crawl.
- The final boss. That's No Moon! indeed.
- What really sells it is Issac's words before the boss fight. Faced with the biggest goddamn necromorph he's ever seen, he utters a simple and quiet sentence, showing us that even after all the horror and abuse he's gone through, Isaac Clarke is not going down without a fight.
- Even better? Isaac rips off his helmet right before the fight proper starts. And you kill it by throwing Markers at its eyes. And after the boss is good and finished? Isaac pulls Carver through its guts and the two of them get up to a control panel to use the Codex. Carver tells Isaac they're going to die, but Isaac knows it means that "Earth gets a tomorrow", and uses it. The two of them get blown off the panel... and Isaac's long battle finally ends. Ellie cries in her shuttle, knowing Isaac is really gone... Or is he?