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In my opinion I will have to go with No More Heroes.

No More Heroes has a lot of things that other 3rd party games don't have:

1. Orignality

2. Great use of the Wii-mote and nunchuk.

3. Great boss battles.

4. A crazy-over-the-top storyline.

5. Travis Touchdown is an awesome protagonist for a game like this. He represents every nerd/otaku out there and you have to love the guy.