If the show opts not to do the whole religious apocalypse thing, perhaps we can look to the rumours of a "Radioactive" theme for intel. Given the fact that our world in reality is dangerously close to all-out nuclear war, I wouldn't be surprised to see it play out like this in the show.
Of course, we'd still have to contend with the Coven and Murder House connections, but I'm envisioning it like this: the season starts with a cataclysmic nuclear event. Then, in the aftermath, we see the destruction of the human race as we know it. Maybe the witches will take advantage of the chaos to seize control once and for all.