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Despair of the Endless is a DC cosmic-entity made famous in her portrayal in the Sandman comics - although not a true villain she is arguably a negative (if necessary) part of the universe thus should be included in the realm of villainy if only for that fact: she is also said to be behind many events that are evil by human standards of morality due to her very nature.
Despair is the near-omnipotent embodiment of both despair and hope, since neither can exist without the other - she takes the form of a rather unattractive female with sharp teeth and an almost albino appearance and is notable for not wearing clothing: she specialises in causing people to fall into despair and was said to have been worshipped at some point in human history until her followers killed themselves.
It is also worth noting that the Despair shown in the Sandman comics was not the original entity but rather took its place - making her the second being to take on the role (since despair is a constant part of existence whoever kills an aspect of it is doomed to become it).
Her realm is populated solely by her pet rats and is decorated with countless mirrors through which she gazes upon people who are in despair and she has shown signs of self-mutilation as she habitually carves her own flesh using a ring with a hook attached to it: although Despair doesn't speak very often she is not always seen as hostile and has hinted at affection for her family - especially Delirium and has been shown to miss Destruction (perhaps because these two abstracts are, arguably, linked with her own aspect).