In the earlier stages of the game, there are a few cabinets of the original Area 51 arcade game, complete with red and blue light-guns.
Defeating Grays
To defeat Grays that use shields, mutate and fire parasites at them. It will bring down the shields faster than any other weapon in the game.
Defeating the Super Beast
When fighting the Super Beast, rather than running straight at him, run around in a circle. When he gets near an explosive barrel, shoot it. It does more damage then the BBG. Watch out for his plasma shooting arm as well. When you finish, Edgar will talk to you, and you get to see him.
Defeating the Thetas
The best way to defeat a Theta is to first mutate. Next, fire parasites; or if you want to take a chance, fire contagion to lay some heavy damage on him. Use contagion for heavy damage, but parasites also work well, especially because they heal you. When your mutagen runs low, run up and melee him and the enemies he releases on you. Keep doing this and he will eventually go down. This will take some time to accomplish and may be difficult at first.
Hard difficulty
Complete the game on normal difficulty to unlock the hard difficulty.
Interesting scans
During the training levels, scan everyone that you can. You will find some interesting equipment of the MPs, including adult diapers and condoms.
Moon Landing Conspiracy
When you reach "Lies of the Past: Checkpoint 4", you will ascend in an elevator. Exiting the elevator, you will see a replica of the Moon's surface, a model of the U.S. space suit, and a shuttle the United States used to reach the Moon. This is in reference to the Moon Landing Conspiracy, claiming that the U.S. never actually reached the Moon, and faked the landing to beat the Russians in the space race. The conspiracy was heavily debated, but ultimately rejected by the majority of opinions. Today, only a few people still claim the Moon landing was a hoax.
Sharks with machine gun heads
In the level "The Grays" proceed into the 4th room in the level, where you can see the monorail you entered the level from out the window. Push the computer console there and it will say "Lifter activated". Make your way back outside to the monorail, you can now stand on it. Run all the way to the back of it and you will be warped to a weird room with sharks that have machine guns attached to their heads.
Unlock Final Secret
Grab all the other secrets to unlock the final secret.
Unlock the Alien Multi-player Avatar
Beat the Campaign mode on the Hard difficulty setting to unlock an alien Gray as a selectable multi-player avatar.
Unlocking Secret Tapes
Scanning all five databank items in each stage yields one secret. Completing the game yields one secret.
Upgrading The Alien Grenade
In the stage Life or Death, there is a small key on a dead soldier in one of the lifts where Cole starts the stage. Grab it to open the small lockers in the stage. One of the small lockers in the first power conduit pit has a databank item that upgrades the alien grenade.