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Somehow, my last message got lost (I think SF was down, and
I never got back to retype it), sorry.

I disagree that the pyconfig.h.in change has no effect on
other platforms: it will affect any system that either
defines __BIG_ENDIAN__ or __LITTLE_ENDIAN__, e.g. gcc on
Itanium. Not a big problem, since it should be conceptually
correct on all systems where it is defined.

However, the real problem is that you are editing
pyconfig.h.in. This is a generated file, and your change is
lost the next time somebody runs autoheader. Please use
AH_VERBATIM to define the block to be generated for
WORDS_BIGENDIAN.

I can understand that you cannot use sys.byteorder. That
doesn't mean osxconfig.h is required, though: If pyconfig.h
already solves the problem, we should use that, instead of
duplicating it. For example, you could write a
expat_config.h which has

#include <pyconfig.h>
#ifdef WORDS_BIGENDIAN
#define BYTEORDER 4321
#else
#define BYTEORDER 1234
#endif
#define XML_NS 1
#define XML_DTD 1
#define XML_CONTEXT_BYTES 1024

and then just define HAVE_EXPAT_CONFIG_H in setup.py