Two big, unanswerable questions are:
1. What is consciousness?
2. Is randomness is an essential feature of nature? Or, is it merely an expression of our lack of knowledge?
The first question, about consciousness, boils down to asking how unthinking matter can think.
What I mean by the second, which is about randomness, is this. When, for example, we lay odds that it will rain 30 days from now, do the odds reflect our lack of knowledge about what is already destined to happen? Or, rather, is the future weather not known yet even "in the mind of God," so to speak?
Given that we don't have a solution to either of those two, essential questions, how well-grounded can any of our knowledge of other things be? Obviously, I mean philosophically. (As a practical matter, I am not too worried that my chair is about to collapse through the floor.)
The most useful thing I have read about consciousness comes from Erwin Schrodinger, the physicist. Trying, I think, to get us comfortable with the idea that we will never figure out what consciousness is, he likens consciousness to, essentially, a camera that can take pictures of anything around it, but not of itself. (Even with a mirror, you cannot get a picture of the chamber inside, where the action is.) But being unable to see the inside of the camera is a pretty small price to pay for all the great things you can do with it, so, we should just enjoy using it, and stop complaining about the one thing it cannot render. Put a bit differently: to be able to look at matter, you have to write yourself (your mind) out of the picture.
Consciousness-as-camera may be either Schrodinger's metaphor, or my own attempt to summarize what he was saying in other ways. I can't recall (and do not have time to research it). The insight is his, however, not mine. There are passages of this kind in his book, Science and Humanism, which I recommend, and would take with me to a desert island. I also recommend the Entitled Opinions episode on Schrodinger, which you can find elsewhere online.
[Edited 10/30/12.]