In Othello and other plays by Shakespeare, it is difficult to isolate any single theme or idea as the main message. Most readers and audiences will agree that it is a good thing not to trust appearances without doing some investigation and that the plot of Othello demonstrates this fact. Othello is easily tricked by Iago's appearance of friendship and loyalty to him and by the appearance of things Iago has manipulated, such as the missing handkerchief. (In this case it is more of a disappearance.) But these things are more the result of other factors that represent the deeper themes of the play.
Iago's acts of deception are effective because Othello is too virtuous to even consider that a trusted friend would lie to him. In general, those who are honest and decent toward others have difficulty believing that there are people who tells lies just for the sake of lying and that there are people who have no qualms about doing evil things, even when there is evidence of it. To me, this is more thematically important to the play than the idea of not trusting appearances, though one could say that the two ideas are related.
Though many commentators have downplayed this aspect of the play because it is a sensitive issue, Othello's status as "the other," an outsider in the European culture, is also a major theme. Iago exploits Othello's sensitivity based on that status, and the catastrophe that concludes the play is a result of Iago's own racial hatred, as well as Othello's insecurity. Again, "not trusting appearances" is a good idea, but the meaning of Shakespeare's play goes much deeper than this.