I suspect you are not even getting the question quite right. Many of Shakespeare's characters have a "fatal flaw"(e.g. Othello's jealousy), but that concept is not normally applied to his work as a whole.
Shakespeare is the most famous dramatist of the world. He is one of those dramatist who not only touched all forms of drama- tragedy, comdey and history, but also left a milestone in every genre. His four greatest tragedies are Macebeth, Hamlet, Othello and King Lear. The protagonists of the dramas are heroes. All heroes have the quality that further proves their flaw. I mean that their best quality, their greatness causes their ruins and downfall; sometimes even death as in the case of Macebeth. For example Macbeth's (protagonists' name) fatal flaw was his vaulting ambition.While hamlet was always found himself in "to be or not be". In this way, their best quality is ultimately their weakness that leads them to their downfall. This is the tragic flaw of Shakespeare's heroes or you can say of his dramas.
There is a big difference between anti-hero and villain. Shylock was one of the important characters as if he were not there. May be the drama was not possible. Tragic flaw has nothing to do with the characters of comedy.