I always loved the Needler from the Halo series. It was a really unique design at the time and probably the most fun I've had with any weapon in a first person shooter. Also, the explosions and the ching it does when reloading are just perfect.

I really like the Aperture Labs portal gun.

The pod gun from Fifth Element is one of the most interesting from both a design and an effects perspective IMO.

Deckard’s gun in Blade Runner was always my favorite. Somewhat uncanny because it was clearly sci-fi, but retained that hard boiled detective aesthetic, like you misremembered a noir shootout.

Noisy Cricket

I have way too little knowledge about the genre in general but there was something oddly satisfying about the Service Weapon a.k.a. Director’s Gun from the Federal Bureau od Control..

But I am guessing the part of using it as a game mechanic makes a big difference, there were plenty cool looking things in movies or series — but this one just jumped first to my mind.

They crazy gun from The Fifth Element.

Fuck. Too many choices bru.

Halo's OG AR, the MA5B has that utilitarian look to it, like the rest of that universe. I like that because it feels realistic in a way (think of the utilitarian designs to the armor and vehicles in Aliens, for example.)

The railguns in Eraser, with their oversized x-ray scopes. Nothing special in retrospect, but I thought they were awesome when I saw the movie in theaters.

Weta Workshop has put out some cool-looking stuff. The Chemrail in Elysium for instance. Although, I think I'm more enamored with the in-universe lore of it. From the fandom page:

It is a dual-stage weapon, use chemical propellant first and then electromagnetic rails as the second stage.

Pretty cool actuation! That and the Lightning Gun from Unreal Tournament 2003/2004 are the only two with memorable (lore-wise) firing mechanisms for me. Here's the Lightning Gun's:

Once the target has been acquired, the operator depresses the trigger, painting a proton "patch" on the target. Milliseconds later the rifle emits a high voltage arc of electricity, which seeks out the charge differential and annihilates the target.

Design-wise though, I think Weta's weapons in District 9 were more appealing—more exotic, u noe? E.g., the ARC gun, and the Repeater.

I think the District 9 designs must have influenced the weapon design in the Titanfall franchise too, and I like the weapon designs there as well. The Flatline is maybe my favorite pilot weapon design (not to use though). Charge Rifle is pretty cool too though, with the 'breathing' capacitor banks on the sides. Titan-wise, gotta be Tone's cannon, hands down.

But there's so many more!

I'm rather fond of Murphy's burst-fire pistol and hide-away leg holster in Robocop. If we are talking the coolest gun, it's got to be the Zorg ZF-1 from the Fifth Element.
https://grabcad.com/library/zorg-zf-1-with-shutters-1

I want to toss the Type-2 phaser from Star Trek (circa 24th century) as my personal favorite. It has this design which reads as a tool more than a weapon, which I love.

I’m partial to the Judges’ guns, particularly from the Urban-led movie, as I’ve not delved much into the comics.

Also, I think this falls more into the fantasy category, but I love the chonkiness of Hellboy’s Samaritan.

Zat'nik'tel from Stargate SG:1.

First shot stuns. Second shot kills. Third shot disintegrates.

Since I haven't seen it mentioned yet, the M56 Smartgun from Aliens is pretty awesome.

The iconic and tastefully restrained design of the Blade Runner handgun https://www.imfdb.org/wiki/(Blade_Runner)_-_LAPD_2019_Blaster

I don't know if anime counts, but the Psycho-Pass "Dominator" is a really cool science fiction concept in itself.

Someone needs to go through and add inline images to each of these

I'll always have a deep love for the Caster from Outlaw Star!

Big beefy wizard gun with huge chonky bullets that shoot magic spells, what more could you want?

The Callahan Full-bore Autolock "Vera"

It’s simple but sleek - the WESTAR-34 blaster pistol that Jango Fett uses in SW Ep 2.

Also looking up the name made me realize that this website exists…seems like an IMDB wiki of movie weapons:

https://www.imfdb.org/wiki/Star_Wars:_The_Prequel_Trilogy

A couple that come to mind:

Boltguns, and esspecially the bolt rifle from Warhammer 40k - specifically because its so massive and brutalist in design to look intimidating.

Ar-2 from Half-Life 2, for the more grounded yet still entirely sci-fi look.

Finally, the Shard Gun from Xcom 2

The Laptop Gun from Perfect Dark

Spetsdöd.

I guarantee you've never heard of it because it only appears in a series of novels by Steve Perry, the Matador books.

The gag is, it glues to the back of your hand. The barrel runs along your index finger, and you fire it by pointing your finger and touching the barrel tip with your fingernail.

It fires microdarts which can have a variety of effects, the #1 use being a drug called "Spasm" which makes every muscle in the body contract involuntarily, leaving the victim tied in a knot for 6 months.

The original trilogy of books:

The Man Who Never Missed
Matadora
The Machiavelli Interface

Then solo books after:

The Albino Knife
Black Steel
Brother Death
Churl

Prequels:

Omega Cage
The 97th Step
The Musashi Flex

phasers

From a novel so you don’t get to actually see it, but the clockwork diamond pistol from Chasm City always caught my imagination. Mostly transparent and needs to be key-wound.

I was an eldar player back when I played WH40k, but the tau railguns are such a great bit of visual design. Perhaps amplified by how terrifying they are to be on the receiving end of.

I'm going OG - the Buck Rogers disintegrator gun.
(See: Foo Fighters self titled release)

I'll take the boring route. I respect the gun design of the N7 weapons. They look like futuristic versions of our current weapons but the paint design is on point.

All the Warhammer 40k guns are pretty thick.

As much as I didn't like the game, the MagX guns in Starfield are pretty dope.

The flesh guns in eXistenZe are also pretty rad.

The Zorg gun is cool, but I always liked Judge Dredd's more. All the same multivariety of fire modes, but in a compact handheld design.

Destiny 2 has some great ones. I always liked the design of the Sleeper Simulant.

For me it has to be the PPG from Babylon 5, it is small, but looks like it has some weight to it.