Okami
Okami is an incredibly unique game in every way, and it uses its setting to its advantage. Okami is still visually striking ten years after its release, but was even more impressive in 2006.
The game features a distinct cel-shaded style that almost looks like a beautiful Japanese painting. Most of the themes in Okami deal with Japanese folklore and mythology, and that look seeps from every facet of the game. One of the integral gameplay pieces involves using a brush to draw symbols on the screen to enact miracles.
The main character, Amaterasu, is a Shinto sun goddess that takes the form of a wolf. In Okami she sports a giant flaming disc on her back. Amaterasu fits perfectly in the world, and her movements almost flow through the ink style painting. Okami is one of the most gorgeous games ever made, and something that remains wholly unique to this day.