Hi Tim,
The "Layout Only" feature is a relatively new one introduced since the context menu adjustments (in the PDF Viewer) became possible. The idea is that PTXprint shouldn't need to re-process all the USFM data through a complex set of transformations every time a user adjusts a paragraph (grow by a line, or shrink to fit, etc.); so it just runs the layout part (XeTeX) of the process.
When "Layout Only" is unchecked, the sequence is: Processing -> Laying Out -> Finalizing

When "Layout Only" is checked, the sequence is: Processing -> Laying Out -> Finalizing

If on the other hand you make a change to certain settings, then the data has to be (re-)processed, and it automatically detects that and does so (notice the third [-] state that the checkbox takes temporarily for the 1st run after settings have changed). It is also smart enough to notice if the USFM files in Paratext have been updated since the last print run and ensures that they get (re-)processed. So, in theory this all "just works".
If you are paranoid about it missing an update, then just leave that "Layout Only" option unchecked and wait the extra few seconds each time you hit Print.
One caveat you need to know about: PTXprint does NOT update the PicList automatically. So if you change details (like the caption, or the illustration itself) in the Paratext files, then you will need to visit the Pictures tab and update things there.
I hope this helps you understand how it works. We are in the process of updating the "documentation" which is primarily in the Tooltips, and also in the MASTER SLIDES which are also being updated in preparation for an upcoming training event at EMDC next month.