This is a difficult question to answer because, in the truest senses of the word, each literary work, including Paradise Lost, is “unique” (one of a kind). If any work is examined closely enough, any work will necessarily seem “unique” unless it is simply a carbon copy of some other work.
Paradise Lost is highly distinctive in the history of epic poems partly because it uses the English language to combine classical literary influences, especially the Iliad and the Odyssey, with fundamentally Christian ideas and a fundamentally Christian message. No talented poet before Milton had ever done quite the same thing in English, and no great poet has done anything in English in quite the same way since.
Also making Milton’s epic highly unusual, both before his era and afterwards, is the way it draws on the Bible so explicitly for so much of its plot and characterization. And yet Milton also, of course, expands enormously on the basic Biblical story – another feat that few poets in English have attempted since Milton’s time.