The Church
There's no real debate that the biggest image of the supernatural world shaking up the world of the living is a huge portal into another dimension that's created by Gozer and its pet terror dogs. Being the Destructor, Gozer's whole purpose is to pop by the mortal plane every so often and cause as much damage as possible. Gozer is a god of chaos and therefore inherently represents all the supernatural havoc that the movie has been teasing at this entire time.
One of most memorable images of Gozer's destructiveness is probably when, in the form of the Stay Puft Marshmallow Man, the Destructor crushes a church. Venkman even gets upset about this, saying that nobody crushes a church in his town. The church is just another symbol of order that's being squashed by the supernatural.
What probably makes the church's destruction the most disturbing is that as a symbol of organized religion, the church represents a human understanding of the supernatural. Followers think they've got the great beyond all figured out, but the Bible doesn't say anything about giant marshmallow men turning churches into pancakes.