American actor Harry Hamlin, who portrayed the Greek mythological hero Perseus in the 1981 film Clash of the Titans, reprised the role almost 26 years later in God of War II. According to Hamlin during a GameSpot interview on the game's launch day, the developers wanted him to recreate his role in the original film, as he thought they "saw some value in having Perseus or a Perseus-like character" due to his unique arsenal. He also felt the game's wide-spanning use of the Greek mythos was similar to the approach taken by Clash of the Titan's filmmakers, and that the film's longevity factored into him being asked to reprise the character. He was convinced to take the role by his next-door neighbor, who worked as a trailer editor for the series and showed him some of the first God of War game for context.

The voice actor for "Bath-House Girl 2" from the sex minigame also plays the role of the mom in the Disney Channel family sitcom "Good Luck Charlie".

Aphrodite is labelled as a character in the game's instruction manual, but doesn't make an appearance until God of War III.

David Jaffe said that they did not want to include the Roman numeral number two (II) in the title because they did not view God of War II as a sequel, but a continuation of the previous game. However, they did not want the title to convey the impression it was an expansion pack.

There is a hidden message after the Perseus boss battle. Stepping on the three white stars with Kratos' left foot and heading back to the tree directly behind the Reins of Chaos will cause Kratos to start absorbing red orbs from the tree. As this happens, a message will be written in the sky.

The message reads "Now I am become death, the destroyer of worlds." This is a line taken from the Bhagavad Gita, a piece of Hindu scripture famously quoted by J. Robert Oppenheimer after witnessing the detonation of the first nuclear weapon in 1945.