The Artemis laser gun in Devil May Cry 3
Guns are ridiculously weak in DMC3. Cutscenes make them look like Alucard's guns in Hellsing, but ingame, you may as well shoot peas. You need them against some enemy types and they can have their uses in combos (to keep you and the enemies in the air, or to blast them away).
The Artemis gun is entirely useless unless you use Gunslinger style, which gives you alternate fire modes, but makes your attacks and defense vastly rely on two different guns. You can then stagger WEAKER enemies at a delay. IF you time it right. That's it. It looks dumb, it does almost no damage, and any other gun is a better choice.
The plasma gun in Deus Ex Human Revolution
I loved this thing in DX1 and screamed like a little girl when I got it. Potentially, it may be the best gun in the game, but it's without a doubt the worst by far since you get it shortly before the end of the game.
Most enemies at this stage are a joke and can't shoot back. Your fully upgraded PISTOL can kill them in 1-2 bodyshots, the plasma gun takes around 3-6 because you get almost no upgrades that far in the game. If you even use big guns, you'll already have a much more powerful one, and you'll have to sacrifice quite a lot to make space for the plasma gun.
If you carried one of the rare weapon cooler upgrades around for ages, this is the one other gun you could use it on. With it, it looks even more awesome, but thanks to the clipsize, you're forced to reload all the time and won't even get to overheat it. Not that the entire game gave you nearly enough ammo to use it more than three times.
On the plus side, it looks the most badass. What a shame.