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First referenced in chapter 21 with the quote "a cloaked man wrapped in cloth who looked somewhat different from the rest," Nephilim are a Species of creature, atleast one of which was implied by Memeta to be directly granted directives by Crypto.  The Nephilim referenced above is known to have been named Samayael due to Ethan's use of Analyze, and was the subject of the Corruption status effect, which ceased all health and mana regeneration as by the following quote: "Your soul is corrupt. You may no longer regenerate health and mana. Your appearance is altered."  The implied mission granted to Samayael by Crypto can be presumed to be for the purpose of keeping the knowledge of Runic magic from mortal beings.

[As of the time of writing this, there are 44 instances of the word Nephilim in the text of the story.]