Auto-Revive: You have a self-revive that recharges over time.
Arkfall Breaking Bug: A current problem that can come up is that sometimes, during major Arkfalls, one of the smaller ones won't complete despite the objective being completed, therefore making the Arkfall unable to be completed, making everyone's efforts useless.
Big Damn Heroes: The Arkfall system turns players into this. During major Arkfalls the first stage is four or more smaller events, it's quite common for a single or pair of players to be trying to hold the line at one and be reinforced by two dozen players riding in on ATVs, dune buggys, and Dodge Challengers.
Can also be something of a subversion as well: One player who knows what they're doing is easily capable of beating a minor Arkfall challenge. The two dozen cavalry who ride in to the rescue then subsequently turn all the enemies into outright bullet sponges with orders of magnitude more health than they used to have.
Body Horror: The result of getting hit and killed by an Infector.
Broken Bridge: At what's left of the Golden Gate Bridge, there is a very large mech. Getting too close gets you blown to hell. Eventually you get access to an ICBM that blows it to bits, letting you advance into what's left of San Francisco.
Bug War: Anytime a large Arkfall occurs with the primary enemies being hellbugs. Expect battle zones to be filled with car sized bugs duking it out with literally dozens of ark hunters.
Crapsack World: In comparison to the show, which has more of a hopeful wild-west vibe, the game's setting (the San Francisco Bay area) has an incredibly hostile environment that one could be forgiven for thinking takes place in a more destructive After the End type scenario.
Car Fu: You can kill most low level enemies by running them over. It even levels up your driving skill with that vehicle type!
Cybernetics Eat Your Soul: 99ers, a group of miners, turned psychotic after getting cybernetic implants - replacing more and more of themselves until they were over eighty percent machinery. It's implied the original psychosis came from an external third party, however.
Cycle of Hurting: Grenade launcher using enemies can do this to you if you're not careful and stand still when fighting them.
Enemy Civil War: Each of the enemy factions in Defiance represents a different extreme, so you're bound to occasionally catch a break when the bugs and raiders kill each other instead of you. Hellbugs are animalistic and hated by everybody (it doesn't help that they're the game's Goddamned Bats), mutants are human supremacists who have ironically and tragically gone insane from the transformation from earth defenders to mutated junkies, raiders are multiracial bandits who like to kill everyone for scrip, Dark Matter is Defiance's version of The Thalmor and make deals with the other factions only to backstab them constantly, the 99ers are cyborg miners who have gone insane, the Volge are blood knights who want to conquer everyone, the afflicted are The Infected, and the Grid are The Borg. You've got every type of basic enemy and they all hate each other almost as much as they hate YOU. Meanwhile, your boss is trying to terraform the planet back to the way it was, save the earth, and commit mass genocide to stop the Crapsack World you constantly fight in. That makes you the villain protagonist who saves the weak and kills everyone else, so it's no surprise that enemies will prioritize ark hunters, yet still have to fight each other due to irreconcilable differences.
Gameplay and Story Segregation: the shields in the game can take a LOT of damage, and even heal your character while at full. In the TV series, if there are any shields, they don't do much good for Defiance or its enemies; Volge die instantly from a few regular headshots, when in the game the Volge shield is one of the most stable and enduring. Also, Armored Hellbugs in the TV series are REALLY easy to kill (Nathan's pistol kills a smatterling with all the bullets in the clip).
Gravity Barrier: The hills around San Francisco are set up in a way that guides you through the main storyline. A decent vehicle will help you get past them later, if you're interested in scaling them.
Goddamn Bats: THE HELLBUGS. They invade arkfall parties that they don't star in, and then deal serious damage if you don't mow them down. Each of the four types is (relatively) brittle but can stun you long enough for the heavy hitters (bug or otherwise) to take you down:
Small Hellbugs are easy to kill, if you can actually hit them. They skitter around and leap at players, stunning them.
Armored Hellbugs usually have over FIVE armor plates, making any shot that doesn't hit a weak spot Scratch Damage. Any weak spots they have, they can cover. And they explode when they die. The monarchs can DO THE ROLLY POLLY (ouch).
Flying Hellbugs (Archers) are easier to kill, but stay in the background and snipe the player with elemental spit; this is really dangerous when the bugs in question are electric (acutal Interface Screw, disables your HUD) or Tar (slows you down while you're dodging hellbug swarms). And they also explode, in case any of you shotgun fans wanted to do something about them.
And then there's the... things... poking out of the ground; they occasionally spawn with the hellbugs and lay down MORTAR fire.
Half-Human Hybrid: While this trope is implied to happen in the show, the game outright confirms it with the introduction of William Parraba; the first person conceived between a human and a Votan (an Irathient, to be precise).
Healing Shiv: The Bio-Magnetic Gun, or BMG. It can either drain energy from enemies or heal the user and their allies.
Insufferable Genius / It's All About Me: Von Bach all the way. From his introductory scene he paints himself as an arrogant know-it-all, and imposes himself as future savior of Earth due to him having a Ark core. He also repeatedly hits on various female NPCs like Cass Dukar and Ara Shondu, in a manner that suggests they owe him for having the Ark core and being the possible savior of Earth.
Interface Screw: electric-element attacks disable your friendly nanomachine AI. This doesn't kill her, but it prevents you from using the HUD while it's active, including weapon zooming for some reason. AKA, Your game stats (HP, Shields, Ammo, Skill Cooldowns, etc.) are invisible while electrocuted.
Invisible Wall: The dark areas on the map edged with a yellow line are this. Sometimes they don't quite match up.
Monumental Damage: The broken Golden Gate Bridge is shown in loading screens, and eventually, seen in person. Also, there's the fact that everything south of San Francisco and the whole East Bay is uninhabitable, which means that the Bay Bridge, San Mateo Bridge, Dumbarton Bridge, SFO, etc. are all simply gone.
More Dakka: As you progress in the game, your simpler weapons have some crazy counterparts, like a grenade launcher that shoots grenades that blow up into six more grenades, Sub Machine Guns that can unload a fifty round clip in under three seconds, and double-tapping sniper rifles.
Random Number God: The above-mentioned Random Events make the RNG very unforgiving during racing. Since the races take place on open terrain, the random events can interfere, potentially screwing up a Gold Medal time by dropping a Hellbug in your path.
Events will also appear in areas where an open-world PVP Shadow War is occurring, even right on top of one of the control points being fought over.
Short Range Shotgun: Played straight and averted depending on the type of shotgun. Some are slug based and give up straight damage for a considerable range increase, whereas others are effectively useless beyond five feet but kill almost anything dead in one salvo. Still others are essentially misnamed grenade launchers.
Shout-Out: If a weapon looks like it's inspired by District 9, it probably is; according to one of the concept artists, the art director was a huge fan of it.
Unflinching Walk: Subverted and lampshaded. You, Jon Cooper and Torc Mok walk away from a major demolition mission. Torc turns around to look, Jon says that you don't do that only for Torc to ask what's the point of big explosions if you don't enjoy them.
Zombie Apocalypse: The plague from the show supposedly causes this in the game. Jarring in that no such zombies or "afflicted" were in the show.