Here's a top 100 here:
http://www.sciencemag.org/cgi/content/full/309 /5731/78b
My top 4 below
1) There are 4 fundamental forces 2 have been "unified" shown to be 2 aspects of the same thing - can the remaining forces be unified into one grand unified theory
2) The Goldilocks problem - there are a number of fundamental quantities such as the strength of the 4 forces above and nature of the fundamental forces which if they were different would result in a universe with no matter or no stars - are these quantities truely unrelated and how did they get set the way they are? are there other universes with different quantities?
3) How did life first arise in detail. We know that organic molecules can arise from inorganic sources but how did they first concentrate and assemble into the first self- replicating chemicals
4) What is the nature of conciousness? how does the mind work and how does this relate to brain function?