Assuming worst-case input is like assuming that the hacker has to do no work to solve any of these problems, and automatically knows the inputs that will screw with your solution most.
And what do you suggest to assume, instead?
Anyway, most proofs of asymptotic security in cryptography are conditional on conjectures such as "P != NP" or "f is a one-way function".
One of the most interesting debates on Less Wrong that seems like it should be definitively resolvable is the one between Eliezer Yudkowsky, Scott Aaronson, and others on The Weighted Majority Algorithm. I'll reprint the debate here in case anyone wants to comment further on it.
In that post, Eliezer argues that "noise hath no power" (read the post for details). Scott disagreed. He replied:
Eliezer replied:
Scott replied:
And later added:
Eliezer replied:
Scott replied:
And that's where the debate drops off, at least between Eliezer and Scott, at least on that thread.