There's apparently 30 blue medallions hidden away in Leon's, Chris's, and Jake's scenarios (and likely Ada's), making 90+ to find. Shooting medallions may host other awards, but immediately they seem to unlock readable files and figurines.
There's Skill Points and Skills which replace the upgrade and money system which can be fun making a good load-out for your character. Quite a few skills too, and they're all upgradable and require a certain number of skill points in reserve to equip.
The two characters in each campaign actually play pretty different roles. It likely will be worth going through every chapter twice just to see it from both perspective, since there's quite a few moments where the two characters objectives are completely different or they take completely different routes in a stage.
There's Mercenaries Mode of course, and Agent Hunt. Agent Hunt allows you to play the game with two human players playing the, well, humans, and two other players playing some of the random monsters in the campaign.
Once October 2nd comes along, RE.NET will unlock which is sure to add a whole lot of replayability:
http://www.youtube.com/watch?v=QtCkRp_rUT0
And we all know DLC is eventually coming.