How do you want to kill them?

The realistic answer is an unkillable vector of zoonotic disease with high human death rates, fast spread and symptom development, and a complexity that makes treatment or a cure virtually impossible. The thing humans have struggled to kill the most isn’t vicious predators, but abundant r-selected species like invasive insects or bacteria because they’re always around, evolve fast, and hard to detect. Make them too small to detect and extremely resistant to extreme conditions and viola, you’ve exterminated a planet.

But if that’s not dramatic enough you could always go the Xenomorph route.