Without a doubt...Overpopulation! A few years ago, a UN study predicted the Maximum "sustainable" human population would be about 6 billion people. We are already near 8 billion, should reach 9 billion by mid-century, and 12 billion by the end of this century. With automation and robotics taking over many jobs, half the population, in todays wealthier nations, may be living on welfare in another few decades. The changing climate may make food almost unaffordable for millions of the poor.
Sometime in the latter half of this century, there will be one more massive war. It will not be nation vs, nation, but the "Haves" against the "Have Nots". The population will be reduced substantially, and if the Haves win, the world will begin to unite under a common language and government, and mankind will begin a serious "reach for the stars". If the Have Nots win, humanity will revert to the Dark Ages.
None of us will live long enough to see this, but our Grandkids, and beyond, will inherit a world far different than what we know.