I would personally say the Riemann Hypotheis, which has stood the test of time from all the great mathematicians in the last 150 years. Sort of like the mathematician's version of Fermat's Last Theorem, where everyone try to have a crack and gets nowhere. Its result would have a significant impact given much of number theory relies on it as a cornerstone.Actually one of the leading mathematics in the world said that out of all the millennium prize problems, yang-mills theory is probably the hardest!
(I am a number theorist, so undoubtably there would be some bias in my assertion )
While you will get a Fields Medal (if under 40) and a professorship at virtually any university of your choice, is that really what mathematics is about? Recognition and prizes for your hard work is all good, but the primary motivation should be the joy of solving an unknown problem. For the professionals, this should be the reward.