The potential problems are in XAxis.get_tick_space() and YAxis.get_tick_space(). Here is the latter:

    def get_tick_space(self):
        ends = self.axes.transAxes.transform([[0, 0], [0, 1]])
        length = ((ends[1][1] - ends[0][1]) / self.axes.figure.dpi) * 72.0
        tick = self._get_tick(True)
        # Having a spacing of at least 2 just looks good.
        size = tick.label1.get_size() * 2.0
        size *= np.cos(np.deg2rad(tick.label1.get_rotation()))
        return np.floor(length / size)

Consider the last two lines. Presumably the rotation could be 90, in which case the last line would divide by zero. This raises the question of whether the prototype tick rotation ever actually gets set. Tick rotation is set by Figure.autofmt_xaxis, but the rotation angle set there does not end up in the prototype tick. Furthermore, what is the point of modifying the spacing based on the rotation, given that the spacing is calculated here from the prototype tick label font size, not from any expected actual label dimensions?