This is a thought-provoking question. I suppose it depends upon what one means by "powerless."
Are they powerless in a physical sense? That does not seem to be the case. Each of the characters in the novel seems to have a variety of physical powers (from Lennie's massive strength to the sexual attractiveness of Curley's wife).
Are the characters powerless in a mental sense? Again, this does not seem to be the case. Even Lennie has the power to remember a few things, such as his desire to tend the rabbits and hide in the brush.
Are the characters victims of fate? (which I suspect might be lurking behind this question) Well, I myself do not find any indication in the text of the novel that Steinbeck believes in fate/destiny. The words "fate" and "destiny" do not occur in the novel. It seems to me that the characters in the novel have choices, but that there are certain choices that more obviously recommend themselves than other choices.
The most obvious example of this comes at the novel's conclusion when George kills Lennie. Even though Slim tells George that he had to kill Lennie ("You hadda, George. I swear you hadda."), George could have chosen not to kill Lennie.
Even Lennie, when faced with the tempting encounter of Curley's wife, could have managed to follow George's instructions to stay away from her. It was George's choice to remain in the barn with Curley's wife and to move closer to her ("He moved cautiously close to her, until he was right against her.").
So, whereas it may seem as though some of the characters in the novel are powerless, I would argue that they all have some measure of power to choose what it is that they do or do not want.