Probably and Republicans will be too stupid to go with anyone else, hopefully he's on his deathbed by then (if not gone sooner). At least Democrats will have to run somebody else, though not sure who in the current Democrat party would rise to the top. Hillary might make another go at it, but I could see Newsom or Warren going after it as well, but nobody really strong comes to mind.
Ehhh, I'd have thought she had realized that the first go around, however, she actually did win the popular vote against Trump in 2016 (Hillary: 65,853,625 votes (48.0%) vs Trump: 62,985,106 votes (45.9%)), so it's entirely plausible that she doesn't realize that.
I'm assuming you mean when she lost the primary to Barack Obama in 2008. It's hard to argue that it was proof that she was unpopular when Obama went on to win the general election by such a huge margin, and even his reelection by a comfortable margin. It just serves as proof that Obama was extremely popular, moreso than her.
2016, OTOH, showed that the people (through a skewed system) preferred Trump to her. That's a hard reality to dismiss.