Of course, we are only a few years into the 21st century so it is not possible to know what will end up being the biggest foreign policy crisis of this century. To this point, if we are talking about the United States, the biggest foreign policy crisis has surely been the 9/11 terrorist attacks.
In the wake of these terrorist attacks, the US had to determine how to respond. The response needed to be calibrated in such a way that it would keep the US safe in the short term as well as in the long term. It is not clear even today if we have responded in the correct way.
So far, we have been kept safe in the short term. However, we cannot know if our policies will make us safe in the long term. This is the major crisis that we still face. We must somehow keep ourselves safe while, at the same time, acting in ways that do not encourage other countries or their people to want to commit terrorist attacks against us.