Extensive callback interfaces like map() come to mind, where a large number of calls becomes excessively time critical and might thus have made people implement their own special purpose calling code.

However, I don't know any such code (outside of Cython) and I agree that this is such a special optimisation that there can't be many cases. If there are others, they'll likely be using the obvious fallback already, or otherwise just adapt when Py3.6 comes out and move on. The fix isn't complex at all.

I do not consider this a road block.