Will Drupal ever become as popular as Wordpress? (We could list CMS for days but the part that really matters is who needs what and where do they get the most benefit?)
Will medical innovations finally start to defeat cancer? (Several forms have promising research I am fascinated to find out where it goes.)
Is Information Security doomed? Countless companies seem content to do the bare minimum and just worry about damage control when a breach occurs.
The final one to me is what will be the next web innovator?
Should be an exciting year only about 45 more days until we start to answer some of these :)
Did I miss any? Please let me know in the comments.