You've heard it before, but it bears repeating: whether you start on a prologue or Chapter 1, the opening of your novel is important. It's what's going to either hook an agent, a publisher, and a reader or help them decide that your book isn't for them. A good first line is important, but if it's followed by several paragraphs of background information to set up your world or character, you're going to lose us. We want to feel something - shock, amusement, curiosity, fear, excitement - and we want to get invested.
And, in short, it is this:
The first five pages of your novel should be rooted in a scene with a goal and stakes; convey a strong sense of voice, emotion, and setting; either include a catalyst or the promise of one coming soon that's related to the primary conflict and/or include a mystery or question that the reader is invested in.
[Update 6 June 2016] One more thing. If your first five pages contains your main character, then we should also get at least a hint about what internal conflict or flaw s/he will need to overcome in order to triumph in the primary conflict.
I'd love to hear your thoughts on this. Any questions about what I mean? Anything you'd add? Do you know of a novel published within the last five years that hooked you with its beginning but doesn't fit the above description?