Which situation would result in the greatest decrease in human population?

Most probably, the situation of the earth being hit by a comet of the same size that caused the end of the dinosaurs. Scientists think that your best option would be to live around the spot where it hits, because then the end would at least come immediately without you even knowing what hit you.

For those people and places surviving the initial earthquakes, tsunamis and firestorms and the resulting near-total collapse of trade and shipping, industry and infrastructure in most countries the result would be living under a dust cloud that would turn the earth surface almost pitch dark, ice cold (after the last remaining local oil reserves for heating and electricity had been spent) and unable to produce the food that we need to survive for the next thousand years or so. Loss of electricity would of course also mean loss of all those computer-driven or supported services like public services, finance and health care. So that means a starvation / freezing to death-scenario for almost all of the initial survivors. In a situation like that, even the most wildly optimistic estimates put the long-term survival percentage at less than 10% of today's human population.