Mercutio says “a plague o’ both your houses,” what central theme of the play is he voicing? What events before this that make this pronouncement prophetic, and why is it “death” to be...

Predetermined destiny is a major theme in the play, Romeo and Juliet. First offhand, the lovers are considered to be "star-cross'd" which means they are ill-fated from the start.   As mentioned in the prologue, "From ancient grudge break to new mutiny,Where civil blood makes civil hands unclean"(I.I.III-IV), describes how the relationship between the Montagues and Capulets has been so volatile since the dawn of time.   Now, to discuss the events which make " a plague o'both your houses" prophetic:   this statement applies to a series of events after Mercutio's death.   In revenge, Romeo kills Tybalt in a fit of rage and realizes he has become "fortune's fool"(4.1).   Because of this act, Romeo, eventually becomes banished to Mantua.  From there, a series of misfortunes take place:   a plan for Juliet to fake her own death so she can reunited with Romeo goes awry(Romeo never receives the message because Friar John is detained for he is trapped in a black plague quarantine), Romeo decides to take his own life by drinking a poison he gets from the apothecary, Romeo kills Paris in the graveyard on his way to Juliet's tomb, and lastly, Romeo drinks the poison and dies just as Juliet awakes;finally, Juliet stabs herself with a dagger.  Also, we later learn that Romeo's mother has died of grief having learned of her son's banishment.   

All in all, " a plague o' both your houses" begins as a statement from Mercutio because he died dishonorably by his mosted hated foe, Tybalt.  Who was responsible for this?  It was Romeo.  Hence, Mercutio says he has become "worms meat"(4.1).   Shakespeare's series of misforunate events makes this line almost like the climax of the play: from this point on, the audience is exposed to the remaining characters' demises quickly.   

Lastly, the Prince mentioned "Three civil brawls, bred of an airy word,"(Act 1).  So, "disturbances" seem quite routine.  He goes on to mention  the penalty of another fight in public to be death to either parties involved in his speech after the servants fight in Act 1.