Near the end of the Golden Age the Spanish Empire faced cash-flow problems, and military conflict with countries such as England and France.

Piracy at sea weakened the Spanish Empire, as did an outbreak of plaque in the Castilian region that killed over half a million people.

Well there were many factors, each on it's own would not have been sufficient to destroy such a wealthy nation, however the most serious problems would probably be the constant warfare, piracy, religous intolerance (posession of customs and laws that were outdated, in addition to destroying much knowledge and economic insight after the expulsion of the jews and moriscos), ineffective governmental administration and just outright shitty kings ( well at least the later half of the habsburg line)