Great Question setup loads templates, mappings, ingest pipelines, dashboards etc...
metricbeat setup -e
Needs to be run once each time you change the version or change the configuration, like add module, add inputs.etc
Say you install metricbeat on a host and enable the system module... You run metricbeat setup -e ...
You can then install metricbeat on as many servers as you like without running setup because all the config is already loaded.
Then you decide to add the MySQL module you need to run setup again once, and then update the configurations / modules or install on your 10 MySQL hosts.
Then you upgrade a version you need to run setup once again.
Basically once per configuration change independent of how many hosts it is installed on.
Hope that helps.