You can use ORE without any knowledge of Python or QuantLib, yes.
What you will need is familiarity with running command line applications and manipulating XML files. You can use a text editor for this (notepad++ is fine, vi, etc) and there are sometimes XML plugins that can help. Alternatively you can use an XML editor directly (XMLSpy is popular).
Once you can do this, it is straightforward to configure your portfolio and settings (curves, conventions, model parameters, etc) and this is all in the user guide.
Also, if you require support on a commercial basis you can always email firstname.lastname@example.org.