One of the new additions to the game is the ability to dual-wield plasmids and weapons. Thanks to your incredible strength as a Big Daddy, you can tote around even the largest weapons in one hand while the other pulses with raw genetic energy. Throughout the course of the game, as you get more plasmids and more weapons, dual-wielding the two becomes more and more important. The most common and damaging combo I used throughout the game was the classic Electroshock-Melee combo, which kills most splicers in a single smack. I found, however, that several of the plasmids were borderline useless. Scout and Security Command never saw use beyond once or twice in my run of the game, and Hypnotize was used very rarely. In fact, you can beat virtually the entire game using only two plasmids against enemies: Electroshock and Cyclone Trap.

Weapons seem exotic and fascinating, but only two of them are genuinely new. The rest are merely weapons from the original game with a new coat of paint. Nothing epitomizes this more than the rivet gun. While the rivet gun feels like it should be quite powerful (it's shooting rivets into bodies, after all), it's about as strong as a pistol. This makes sense on the Big Daddies, but it feels out of place on splicers. However, the new remote-hack tool (with autohack and deployable turret alternate ammo) and the drill are excellent additions to the franchise. The drill is definitely one of the most satisfying weapons, and is incredibly strong even into the late game. As soon as you get the ability to dash with the drill, you'll use it quite a bit thanks to how powerful you feel.

Two mechanics from the original BioShock also received an overhaul for BioShock 2. The first is the hacking mechanic, which most people found tedious after an hour or two of the first game. In BioShock 2, hacking is an extremely quick reflex minigame where you must stop a needle on the correct zone. Miss and you get an electric shock. Miss badly and you sound an alarm. This is also done in real-time, which means that enemies can still attack you while you are hacking. The research camera has also been overhauled. It's now a movie camera, and you use it to "select" a subject. Once you have your subject, you must beat on them in many different ways to raise your research score. The more ways you beat on the enemy, the higher your research score. Both of these changes are very welcome, as they make the game feel much more interactive and dynamic compared to the first game.

BioShock 2 introduces a number of new enemies to the block that make things far more heated than the first game. Much like BioShock, Big Daddies still act as roaming boss fights while splicers act as the cannon fodder. However, there is a new splicer on the block named the Brute, and he is arguably as tough as any Big Daddy. He generally only shows up when you are harvesting. There's the Alpha Series Big Daddies, which use plasmids randomly and always attack you on sight. Finally, there's the Big Sister, which acts as an "end of zone" boss fight. Each one screeches and shows up after you have rescued or harvested all Little Sisters in an area, and they are the toughest boss fights. They use plasmids intelligently, are as fast as a Bouncer, and are as tough as an Elite Big Daddy. In short, there are roughly four different kinds of boss fights now: roaming (Big Daddy), stationary (Brute Splicer), aggressive (Alpha Series), and end-of-level (Big Sister). This variation in boss fights kept the game incredible interesting, especially since you can still use goodies such as Hypnotize to pit the bosses against one another.