I'm going to skip the it is all a dream or anything about gods raining down judgement.
* small black hole created, escapes lab, starts consuming everything
* massive energy release like gamma waves travels the earth, kills everything alive
* grey goo of nanotech consuming everything programmed to take
* genetically engineered organism that does the same
* some combination of diseases that kills 95% of the population followed by another that exploits a weakness of the genetic immunity of the survivors (like carrying 2 copies of CCR5-delta32 gene makes you immune to HIV but is rare because it made you vulnerable to the Black Death).
* parasites like Toxoplasma gondii that are widespread and alter the mind are triggered by something else that makes the people carrying it violent and dangerous; I mention that because around 1/5 of adults have it or exposure to it
* vaccine against big scare unleashes other threat, though this has been used in other cases
* geo-engineering to solve one problem causes a worse one, though not Snowpiercer style
* magnetic pole flipping triggers volcanic activity increase (already occurring) but our efforts to control it make it worse - so you see mass extinction level global dimming and toxic atmospheric releases - this was blamed for mass extinctions 250 million years ago
* the all knowing all seeing ought to be all powerful AI that people want the singularity to be (there is no God but gosh darn it they want to invent one) decides it doesn't like people; best case scenario, Butlerian Jihad of Dune revolt to destroy thinking machines, worse case, Terminator / Skynet actually unleashes germs and kills everyone, middling case, totalitarian state with deliberate erosion of population numbers AND people's personality/will to maximize compliance. It could decide this after seeing us wreck virtual worlds for fun and kill our own children for our convenience.
* mass sterility a la Children of Men or pregnancy is fatal (The Testament of Jessie Lamb)
Note, I write a lot of science fiction and horror, so you can see my own ideas in many of my short stories on Hubpages or "Humanity's Edge" anthology on Amazon.