I think it's fair to point out that they were never intended to be a good framework for aligning robots and humans. Even in his own stories they lead to problems. They were created precisely to make the point that encoding these things in rules is hard.

As for practical problems they are extremely vague. What counts as harm? Could a robot serve me a burger and fries if that isn't good for my health? By the rules they actually can't even passively allow me to get harmed so should they stop me from eating one? They have to follow human orders but which human? What if orders conflict?