The game (especially the 'Umbrella's End' level) incorporates several elements from the first Resident Evil (2002) movie, such as: the Red Queen computer, an attack on a high-speed train wagon inside the Umbrella complex, the protagonists getting trapped in a room with lasers, etc.
Unlike any other Resident Evil so far, most of the files you collect are profiles of each character and enemy ever appeared in the Resident Evil series leading up to the end of Umbrella.
This is the first Resident Evil where Albert Wesker is a playable character in the main storyline, not including the mini game from CODE: Veronica and the Mercenaries game from Resident Evil 4.
This is the first Resident Evil game released to the Nintendo Wii console.
After the credits, Wesker sits down in the map/satellite room, but if you look carefully on the right side of the map room, you can see the map layout of the castle from Resident Evil 4 (2005), which will occur a year later.