In the Japanese version, the collectible Playboy centerfolds were censored, even though the game was rated "Z" for 18 and above. However the magazine itself in Japan, which ceased publication in 2009, was never censored.

Mafia II holds the Guinness World Record for the "Most "F" Words in a Video Game". The word is mentioned 397 times throughout different instances of the game. The previous placeholder was The House of the Dead: Overkill which featured 200 instances of the word.

However, considering that Mafia II can take roughly 12 hours to beat while The House of the Dead: Overkill takes roughly 4 hours to beat, the latter game technically has a greater concentration of swears in a shorter amount of time than Mafia II.

Many features of the game were cut, but are still in the files. These include buses, drive-bys, difficulty selection, racing, a subway system, taxis and sitting.

The Playboy magazines scattered throughout the game are all anachronistic; the game takes place between 1945 and 1951, but Playboy Magazine was not founded until 1953, and the images placed in the game were published between 1958, seven years after the end of the game, to 1968, seventeen years after the end of the game. The 19 Playboys added in the DLC "Joe's Adventures" range from 1960 to 1969, with a single image added from 2007, fifty-six years after the setting's era.

Each collectable wanted poster depicts a gangster-style mugshot of a member of the game's staff.

The mission "Stairway to Heaven" revisits the events of the epilogue to the first Mafia, adding some details and contradicting others. Tommy's new home is shown to be in Greenfield, Empire Bay, and the two unnamed gunmen are indicated to be Vito Scaletta and Joe Barbaro. The latter shoots Tommy with a Remington Model 870 Field Gun, as opposed to the Lupara used in Mafia, which was not included as a playable weapon in Mafia II.

You were originally able to buy a gun license in the game; however, this feature was cut. The feature was shown in the 8 minute gameplay trailer at Gamescom 2009. Roughly 2 minutes into the gameplay trailer, Vito encounters a police officer. One of the options is "Show your LTC" (License To Carry). Furthermore, there are files still in the game referencing this ability. Additionally, there are files in the game that mention being able buy a gun license from Giuseppe.

The "Seagift Fishing Co." company livery found on the Shubert Truck shows it being operated in three cities - besides the game's setting of Empire Bay, the other two cities are Lost Heaven (the first Mafia game's setting) and Brno (where 2K Games Czech studios are located).

The games files include text referencing multiple endings. During development 2K stated there would be multiple endings, but they were missing from the final version.

The games files include suggestions that a large number of missions went unused. There were also missions that seem to take place during the WWII chapter.

According to leftover text in the games files, it appears that there were originally plans to include some type of fighting club in the game.

There was some sort of job system cut from the game. It involved Vito being able to take jobs from different characters, but not much is left besides dialogue in the game's files.