>>> class Meta(type):
...   def __instancecheck__(self, other):
...     return False
>>> isinstance(3, Meta)

In 2.6, this results in:

Traceback (most recent call last):
  File "<stdin>", line 1, in <module>
RuntimeError: maximum recursion depth exceeded while calling a Python object
(That's a recursion in C, through PyObject_IsInstance and
instancemethod_call)

In 3.0, I get:

Traceback (most recent call last):
  File "<stdin>", line 1, in <module>
TypeError: __instancecheck__() takes exactly 2 positional arguments (1
given)