Want to get users opinion on this topic 
IMO, If you have a setting that needs to be applied at a “system” level(JVM\CLR\wM products etc) i would make an entry in the server.cnf and use it as an extended setting. If there is a need to access a setting for an application\interface that is built using webMethods custom code i would prefer to use a global variable. An example would be From email address for the server or email hostname which can be used by all interfaces to send out emails.
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Yes each has its own advantages and I believe application/system level global changes and so there would be no conflicts! :)-
HTH,
RMG