I think there are three big questions:

1- Why is there something as opposed to nothing?
Given that there is something, we have physics and chemistry
and thermodynamics to describe it. 

But then
2- Why is there life?
The universe could well exist with inert planets revolving around
stars, there could be weather and earthquakes and activity easily
explained. by the above mentioned sciences. But what is the force that 
drives disorder backwards? How does a tree suck up water? How does a 
dog know to salivate? So given that there is life, we 
have biology to explain it. 

But then
3- Why is there human life?
Why are there creatures who not only survive and procreate, but who have
fun and get mad and build machines so they can get places real fast?
So we have psychology to explain people.

And now I can think of the fourth question, which is really the main
question that needs to be answered
4- Why is there me?
Even if I am not special I am at least unique in that I am the only
vantage point that I have to observe everything. And why am I sitting 
in the middle of all this stuff not only experiencing it
but actively participating and changing it? 

Why am I so curious that this question nags at me?