Gameplay-wise, some key differences between DC and UC include:
There is now a reloading animation shown on-screen that displays the character's current weapon being reloaded.
Grenades must be equipped before being thrown, they are not always in the inventory anymore.
The perfect headshot hitbox is much smaller than it was in UC, and it will still get smaller the higher the difficulty is.
There is a new "Title" system in the game, these are small in-game achievements the player can earn by performing certain actions a number of times. Files also make a return to the game, this time including many more items to collect.
There are now costumes the player can unlock after certain conditions are met.
While Umbrella Chronicles featured a way to unlock infinite ammo to all weapons by getting an S rank on all chapters in Hard mode, Darkside Chronicles has no way to turn on a global infinite ammo and the only weapons with it in the game are the Handgun and Linear Launcher.
The "Star" mechanic that serves as a way to upgrade weapons has been ditched and instead replaced with a Gold mechanic where the player earns gold by destroying objects on the stage or picking Gold up in the environment.
There is a hidden "coin shoot" mechanic where, if an object is shot and a coin (Gold) is dropped, the player can keep shooting the coins to gain a huge stack on coins, there is a limit to how much Gold can be earned this way, but it's possible to get at least 5000+ Gold from just one coin.
There is also a hidden mechanic related to perfect headshots, where performing a perfect headshot while low on health gives more points than one done on full health.
The "Objects Destroyed" requirement in the Results screen has been ditched and instead replaced with a "point" system where destroying objects, killing enemies and getting a perfect headshot gives the player points.
Additionally, performing multiple perfect headshots in a row gives more bonus points as it can be seen by the red text that appears on the screen. (which is also new in DC)
Your partner's health bar will appear on screen even in solo mode and they can die as well.
When it comes to regional differences, the most notable one is how the game was censored in Japan, with perfect headshots not blowing off the enemy's head, but still making the same sound. The red text still shows up on-screen which is another good way to indicate it.
In this mode, Claire Redfield is the only playable character and there is no way to play it on co-op. All enemies are replaced with Tofu that are aggressive against the player. The objective is to reach the Shopping district west while starting from the Police station front entrance with only a Handgun and Knife. There are no healing items or checkpoints in this mode, making it perhaps the hardest part of the game.