Unless P=NP, I don't think it's obvious that such a simulation could be built to be perfectly (to the limits of human science) indistinguishable from the original system being simulated. There are a lot of results which are easy to verify but arbitrarily hard to compute, and we encounter plenty of them in nature and physics. I suppose the simulators could be futzing with our brains to make us think we were verifying incorrect results, but now we're alarmingly close to solipsism again.
I guess one way to to test this hypothesis would be to try to construct a system with easy-to-verify but arbitrarily-hard-to-compute behavior ("Project: Piss Off God"), and then scrupulously observe its behavior. Then we could keep making it more expensive until we got to a system that really shouldn't be practically computable in our universe. If nothing interesting happens, then we have evidence that either we aren't in a simulation, or P=NP.
, or the simulating entity has mindbogglingly large amounts of computational power. But yes, it would rule out broad classes of simulating agents.
Jonathan Birch recently published an interesting critique of Bostrom's simulation argument. Here's the abstract:
The paper is behind a paywall, but I have uploaded it to my shared Dropbox folder, here.
EDIT: I emailed the author and am glad to see that he's decided to participate in the discussion below.