I suppose the option to put files and apps in the location of your choice appeals to all users; certainly to those used to organize their stuff as they see fit, as was possible in Classic/Mac OS 9 and earlier. Unfortunately, Apple as well as other software publishers (following Apple's recommendations) not only prefer apps to be in the Application folder, they may require it for proper operation. This is why most installers place apps in the Application folder by default and don't offer alternative options.
When you don't adhere to this location requirement, affected apps may 'misbehave'. It is hard to predict the kind of misbehavior that will most likely follow, or even exactly when that will happen. AFAIAC when it happens at all I tend to see it when trying to run updaters: occasionally these fail.
Apart from System issues, the reason is usually either the fact that the affected apps are not in the Application folder, or they are there but have been changed from their default condition. The latter can occur e.g., by changing the name like adding a version number (Adobe Reader, consistently), or by combining them with associated files in a subfolder or by taking them out of a default subfolder (MS Office, occasionally).
