Files (±50MB, audio) automatically repetitively deleted (after ± a couple of hours-days?)
Does this has something to do with CRON (just a wild guess)? 


No, drupal won't delete files in the folder, it must be something else on your server.


  Is it not smart to manually (FTP) upload files into the root folder? Should a module be used at all times?


Files should be in your files directory (usually sites/default/files) if you're uploading them via the UI so Drupal can manage them.  If they're more static, they should be in a module/theme folder.