This looks interesting and is very similar to what I've been working on. I could be missing something, but from what I can tell queries on related tables won't get invalidated. For example:

profile = Profile.objects.filter(user__username="test")

should get invalidated when either profile or user are saved/deleted, but I think this would only invalidate when profile is saved/deleted.

Also, the post_save and post_delete signals won't get fired on queryset.update, so if I were to do something like Profile.objects.filter(user__username="test").update(username="something else")

then Profile.objects.filter(user__username="test") will return a stale object. You could override the queryset's update method, but you'd still have the same problem as above with related models.