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stack_pointer isn't a register because its address is taken at two places.  This is a really bad idea for optimization.  Instead of &stack_pointer, we should do:

PyObject **sp = stack_pointer;
... use &sp ...
stack_pointer = sp;

I'm pretty sure this simple change along with a 'register' declaration of stack_pointer gives a good speed-up on all architectures with plenty of registers.

For PCs I've experimented with forcing one or two locals into specific registers, with the gcc syntax  asm("esi"), asm("ebx"), etc.  Forcing stack_pointer and next_instr gives another 3-4% of improvement.

Next step is to see if this can be done with #if's for common compilers beside gcc.