http://bugs.winehq.org/show_bug.cgi?id=6233
--- Comment #11 from Frédéric Delanoy frederic.delanoy@gmail.com --- (In reply to Rosanne DiMesio from comment #10)
Perhaps it wasn't there when this bug was filed, but the Applications tab currently states at the top "This tab is linked to the Libraries and Graphics tabs to allow you to change system-wide or per-application settings in those tabs as well."
As is, it looks like only the "windows version" is selectable for each application IMHO.
In the six years I've been on the forum, no one has ever expressed confusion about it.
That might be because people just don't know about this (it is not mentioned in the FAQ) and just stick to one wineprefix per application. I was confused about it, as did the OP.
However, explanation from comment 1 still holds. The fact one has to say "This tab is linked ..." is a sign that the UI isn't as straightforward/self-explanatory as it should be IMHO.