I think the best reason against simulation is that within the super-universe the simulated minds implemented more directly (e.g. simulated on the level of neurons) and provided with rough VR (akin to some kind of videogame) can enormously outnumber the minds in the simulated universes where it appears as if minds and everything is implemented on laws of physics like ours, in extremely computationally inefficient way like we are (slowdown on at least order of 10^30 i'd say).

If we are in a simulation created by intelligent beings, we should expect (with overwhelming odds) to find ourselves in the universe laws of which were to some extent designed to minimize computational power, even if those universes use up only a very small fraction of computational power used to simulate universes there.

If we are in the universe that simply exists, we should expect to find simplest possible laws of physics that allow for our existence, with no regard whatsoever for minimization of computational power necessary. Our universe looks very much like the latter case and entirely unlike the former case.