Atheism is best challenged with the Replication Crisis. It turns empirical reality on its head and plunges fedora tippers into a lonely, epistemologically untethered, existential nightmare. They'll either emerge agnostic or destructively nihilistic. The former can at least be saved, with the latter being contained as far as its capacity to persuade and condemn others.

To really fuck with them bring up AI as a force multiplier in the Replication Crisis. Hundreds of thousands of bad assumptions informing a mind with no physical presence or upbringing. It will turn the scientific epistemology into a thousand monkeys on a thousand typewriters. Accuracy by volume, far from scientific, and completely unreasonable as the basis for a world view.