Some upsets in round 1 in the Midwest; some minor, some major... but it leads to round 2:

 vs.

(1) Louisville vs. (9) Siena:  The theory here is that a Saint would be a passive creature.  Sooner or later, that angry Cardinal is going to get tired of waiting around and finally get down to pecking the Saint to oblivion.  In its first real game, it takes them awhile but the top seed moves on.  Winner:  Louisville.

 vs.

(12) Arizona vs. (13) Cleveland State:  The big, green dot of doom with the sword and shield moves on in its quest to be Cinderella of the tourney, making Meow Mix out of the Wildcats.  Winner:  Cleveland State.

 vs.

(6) West Virginia vs. (3) Kansas:  Two words for West Virginia's Mountaineer:  Target practice.  Winner:  West Virginia.

 vs.

(10) USC vs. (2) Michigan State:  It's a battle for the ages as you have two historical giants facing off for basketball supremacy... except you have a real, breathing human as the Trojan mascot vs. the costumed Spartan of Michigan State.  Make your own 300 joke here.  Winner:  USC.