Why do presidential employees often leave their positions?

One problem with being a non-elected federal employee is you are prohibited from participating in politics while holding office. At least some of the first term appointments went to election campaign workers who then were not able to participate in the second term campaign. so there is a feeling that they should step aside so the president can reward those that did work on his second term election. In a case like Secretary Clinton, she has to resign in order to be eligible to run for president in 2016.

Traditionally, every term appointees turn in their resignations and are either re appointed or replaced.

Sometimes, they are just tired of the pressure. Sometimes, they have a disagreement with the administration. Sometimes they just want to do something else. The real reasons aren't always known until years later when memoirs are published,

Its a high pressure job , and it wears people out