By default, label and marker symbols stay the same size as you zoom in and out, independent of scale. This results in labels that are frequently too small or too large. This is especially apparent for large format prints.

In order to set a reference scale, first zoom in until you have found a scale that you find satisfactory. Right click the data frame, and choose Set Reference Scale.
(You can clear a reference once it is set but right clicking the data frame and choosing Clear Reference Scale.)