Okay. Here is my scenario...
Hillary Clinton bows out of the 2016 Presidential election following a health crisis (Basically the most generic way I can get her out without changing too much). This blows the lid on the Democratic Party's primaries that year. While candidates like Martin O'Malley, Jim Webb, Lincoln Chafee, Lawrence Lessig, and Bernie Sanders do announce their intentions to run, the lack of a Hillary Clinton not only allows them to perform better in the polls, but it also opens the path to many politicians with ambitions for President to run when they otherwise would not want to challenge Clinton. Andrew Cuomo, Claire McCaskill, Brian Schweitzer, and Christine Gregoire announce in the following weeks their hopes to win the Democratic nomination. The race proves to be just as crowded as the Republican field, and Oprah Winfrey, realizing how much of a threat Trump was, and seeing how ineffective most of these candidates were for the Democratic Party, announced in July 2015 she was running for President.
Already with a dedicated fan base and self-funding her entire campaign to the point that she did not accept any donations, she hoped to make history. With the shock of her announcement still on people's minds at the start of the first debate, she had a breakout performance alongside Senator Bernie Sanders. Despite herself being a leftist, she and Sanders were very cordial with one-another, and supporters who did vote for Sanders saw Oprah as a good alternative. Despite being a close race, Winfrey had the lead for most of the primary season, and over time, she assembled a long list of endorsing politicians. Running on a progressive platform of acceptance, reform, and building on the change Barack Obama began, she hoped to lead a mostly optimistic campaign, and held her attacks on Trump for the primary. Winning the nomination, Oprah announced former NATO commander and Admiral James Stavridis as her running mate, an unusual and unconventional choice that brought much needed military experience to the ticket.
Going into the general election, she faced Trump with stride. Without any scandals trailing her like it would have with Clinton, the Winfrey/Stavridis ticket was optimistic yet serious on issues such as poverty in the United States, and she campaigned in any state she could get, going to Pennsylvania, Michigan, Wisconsin, Iowa, Missouri, and even traveling through the Deep South to rally voters. Without anything to attack her on, Donald Trump resorted to even more dog-whistling and racial innuendos, only further enraging and motivating minority groups to get out and vote. On election day, Oprah Winfrey would be elected to be the 45th President of the United States, taking Arizona, North Carolina, and Georgia while losing Ohio and Iowa.