I have nothing against her as a person or her talent and considerable achievements but Oprah Winfrey has two large strikes against her for being a serious contender for POTUS.
First, she has no experience in government, and this is scarcely the place for On the Job Training. Even in the best of times that is a bad idea and following the correct occupant this nation will need someone with mastery and knowledge in government, diplomacy in all their intricacies to help begin repairing the damage. Some of which may take decades if ever to undo. We cannot trust that to a novice.
Second, the most important characteristic in selecting a person for leadership is judgment. We are not installing someone to simply mirror the public mood, polls can do that, we need someone who can weigh evidence and come to consistent sound conclusions. In many area it would appear that she can do this, but her repeated instances of giving platform and support to pseudo-science and quackery including anti-vaxxer madness, disqualifiers her as clearer as if she were a climate denier. Truly it is the same thing just pushing different crackpot ideologies.
She is a tremendous woman, a talented businessperson, and a passion advocate, but she should never be president.