While there are sure to be things you can't do in Defiance, there will be a bunch you CAN do. For example, and I refer to the fiction surrounding Space Marines here:
Bolters, in WH40K clearly DO NOT fire an armour-piercing semi-guided round that does massive damage and might potentially spray shrapnel over a large area. In Defiance you can make them do that.
Another thing you can do in Defiance is play Tyranids against, say, Waffen SS.
While I am unaware of "weapon kills user" options in Defiance, the statistical derivation of the weapons values means you CAN house-rule in weapons that might not fire; the chance of being denied your attack in this activation is the cost discount for the weapon. So, if you run a 10% chance of the weapon failing to fire regardless of what your to-hit roll was, then you get a 10% discount on the weapon.
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For a close-combat force I personally think you need to back them up with lots of template weapons at range (this seems VERY Tyranid, from my memory of 2nd Ed 40K). Template weapons mess with your enemy's morale, and if you can hit troops that are already shaken or pinned with close combat monsters you can greatly increase your chances of killing 2 or even 3 enemy figures for every monster in one round of close quarters combat. Add cheap Terror CDWs, one-shot cone weapons, or "limited ammo short range high FR" weapons to represent hive mind, fear, acid vomit and other alien horror and suddenly you can VAPORISE entire squads in one round of massive morale failure, let alone the kills you rack up- if you can get close enough.
Of course this is very... VERY high-risk in Defiance, but part of the charm of the game is the speed and degree of turnaround that can occur in just a few minutes in real-time. One fast-mover with a serious cone weapon can really ruin someone's whole day- unless of course they catch it in a crossfire and send it straight to hell.
Compared to the current edition of 40K you'll find you can make troops that move with blinding speed, especially fliers and jumpers which at the extreme may move 24" in one turn- figures large enough to be considered vehicles can use vehicle move brackets that peak at 60" in a single turn. You might need to take advantage of that and Field (ie Invulnerable) saves to help counteract the rather extreme (in 40K terms) quantities of ranged firepower being thrown about- also grenades and CDWs can be built to include "smoke" effects to provide cover for advancing troops and "vehicles".