I suppose if Minato marked Itachi with a seal, he could easily get into his defenses and cause some lethal damage. The Susannoo [sic] is not impregnable afterall.
I say Thanos. While the Flash is definitely the runner up, he'd only be a threat to the world and most likely a superhero would eventually stop him. Thanos on the other hand would be a threat to the Universe, an the only thing that could stop him is his own subconcious desire to be defeated, and that's if it's there this time.
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