Ive always run gun head with frag, spear, Burst HMG, and rail. If you make sure to reload between missions its more than enough firepower

Something I noticed is that Flamethrower seems to perfectly pierce through ANY armor or other kinda defences, so it's pretty helpful against modules with annoying shields like Shuffle or Drone Armor

Tip: You're not obligated to complete bonus objectives. If it doesn't make sense to do it, skip it.

Tip: You can control the weapon drops somewhat by only unlocking the weapons you want.
(After unlocking all the weapons, I deleted my save game, went back and bought only the weapons I liked. Now, 80% of my loot consists of machine guns and nukes.)

Tip: Get the Hazmat Suit, and Nuclear Protective Suit as early as possible. (They'll make you immune to nukes and environmental explosions.)

Tip: Never pass up a Heal Suit, Armor Plating, or Key Generator.

Tip: If you're in a boss fight and getting your ass kicked, throw a few nukes.

My preferred loadout:
Rook Suit (I love a good tank build.)
Two automatic machine guns. (Whatever you pick up will suffice. Module/enemy health bars will drop like a rock.)
I like to keep a few nukes in reserve.
Everything else gets used when it becomes practical to use.

Boss battles favour chunky and powerfull weapons - Railgun, Slugs and shotguns overall. Everything that can quickly strike weak spot.

Passive upgrades stack. You can buy only one and only if you dont have one allready but loot from mission will pile on. Upgrades that add +1s like Armor plates, Key generators, Healing suit are additive but damage, fire rate and stealth seem multiplicative and break game fairly quickly.

Archangels Cutting beam is supreme melee weapon perfect to destroy stations and conserve ammo in general. Its range is small but good enough to cut most enemies safely, damage is strong and it has no ammo limitations of Javelin.

My loadout is:
Machinegun. Any will do even energy blaster but heavier is obviously better.
Smart gun or shotgun to add punch when necessary and help catching flamers, dogs and hornets.
Cutting beam.
Some explosives - AC, mortar, rocket, grenade. All works well when you need to obliterate system quickly and from distance. Great at tearing off Matriarch legs too.