Should I place commas at "A" and "B"? Why?
"One of Shakespeare's greatest comedies(A) Much Ado About Nothing(B) features the wonderful witty war between Beatrice and Benedick."
" That is not what you are trying to say. " But in that case the surrounding sentence is as lame as the other one, and that is not the sentence you are asking about.
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I would put only one at A, making the opening phrase an inverted appositive:
"One of Shakespeare's greatest comedies, Much Ado About Nothing features the wonderful witty war between Beatrice and Benedick."
Two commas make the title parenthetical, which doesn't work because the surrounding sentence becomes "One of Shakespeare's greatest comedies features the wonderful witty