Which is considered as the greatest sorrow as per the Religion?

Greatest sorrow is not the same for all. For Bill Gates having slightest head ache may be the most painful thing. For a poor man in Ethiopia, just being without food for a day may be the greatest sorrow. But this sorrow can be dealt by both these individuals by Bill Gates helping the poor man with a loaf of bread. Islam says the entire life can be lived in perfect Peace of mind by total submission of our Free Will to the Almighty God. How to do this is shown by the Messengers of God and our Last Messenger Prophet Muhammed (peace be upon him) who is No.1 ranked person in the list of Most Influential persons of human history.