@dgelessus - your response is quite practical and greatly appreciated. I probably should not rant on Apple for these difficulties since I do not really know enough about the Framework that the ui module is based on. I have recently been assuming that @omz has put a fairly thin Python binding over the native gui development tools except for the pyui file thing which does not seem to be based on an Apple/objc framework class. I should probably take the time to read about their architecture and how they deal with flexible layouts and widgets in order to see how this maps onto his implementation.
If you have a pointer to a good developer reference that would be good for a Pythonista ui module user - please pass it along. I found this site http://www.raywenderlich.com, which has a 12 part video tutorial on a "autolayout" library. Bad sign that it is a library AND takes 12 videos to say how use it, but it seems very well done.
I think it is worthwhile to explore this from the HTML5/JS angle at this time. There are some Python based projects already out there that attempt to use webviews for their entire UI. @JonB and @ccc have recently enumerated some pain points with doing this in Pythonista in the recent worldmap thread. It is still pretty compelling.
I ran into a project called device.js (https://github.com/borismus/device.js) that gets into many of the issues you mention above and has a sample app "todo list" that works in the webview and changes based on whether you are on a desktop - tablet - phone. The author is currently exploring what this may look like when we have 3D VR glasses as part of our user interfaces - which looks like it may be coming quite soon :-)