There are a few very small incompatible changes - I really doubt most people will ever run into them.
I guess the good news is that we didn't make any big mistakes in the design of earlier versions of Mathematica that we'd have to go back on now.
You kind of alluded to it in your introduction. I mean, for the last 300 or so years, the exact sciences have been dominated by what is really a good idea, which is the idea that one can describe the natural world using mathematical equations.
The most important precedents deal with the whole idea of symbolic programming - the notion of setting up symbolic expressions that can represent anything one wants, and then having functions that operate on both their structure and content.