> Perhaps some mechanism needs to be provided to indicate additional
> processing options per script line:

Sure.  Higery will have to examine existing usage and think about setuptools→packaging transition.  We’ll start simple and easy (in other words, with something very similar to setuptools) and expand from that.

>> Version independence always means version independence in the same
>> major line of development (i.e. X number in X.Y.Z), or to put it
>> another way, version independence among the versions listed as
>> supported in the Trove classifiers.
> That can still be a problem with e.g. byte literals: 2.5 will raise
> SyntaxError where 2.6, 2.7 will not.

If the code is compatible with 2.6+ only, the “2.5” Trove classifier should not be used.  (Maybe I’m misunderstanding your point.)