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I'm hopeful that there will be some announcement of a new Metriod Prime or Zelda title for the Wii U. If Nintendo can offer up a Mario Kart, Super Smash Bros., Metroid Prime, and Zelda for the system, that might be enough to change the tide of red ink for Nintendo. I hope so anyway. There have been reports that Zelda Williams, daughter of Robin Williams, will be at E3 to participate in a Nintendo announcement, so that's a good sign for Zelda fans.
I'm also interested to see what new IPs are in the works for PS4 and XBox One. Destiny is obviously a major cross platform release, but we already know about that and I want to see what is in the works. There may be a new Naughty Dog title (other than Uncharted), and I am ALWAYS excited to see what they can come up with. Both Square Enix and Ubisoft plan some announcements that should be interesting.