Yes, the most pythonic is:
mock(obj, x=1, y=2)
Which you get by:
def __init__(self, obj, **mocks):
self.obj = obj
self.mocks = mocks
This can then also be called (using the built-in double-star-unpacking feature) as:
mock(obj, **{'x': 1, 'y': 2})
or even
mock(obj, **dict([('x', 1), ('y', 2)]))
Then there’s no explicit need to support multiple alternative function signatures, and in particular you don’t get people using the (quite atypical and therefore semantically ambiguous):
mock(obj, 'x', 1, 'y', 2).