I'm not sure it's unique, but the railgun in the Quake series, specifically Quake 2, will always be dear to my heart.

Wabbajack from the Elder Scrolls is a definite contender, but my favorite weapons are the Wunderwaffle DG-2 from CoD World at War and the Thunder Gun from CoD Black Ops.

Despite what everyone says about CoD, the zombie mode from WaW/BO is brilliant and worth the price of admission.

The wrench from the Shock games. Oh, but it is a unique weapon of choice indeed. Such a mere tool can easily be used as a deadly weapon against the evils of space or the sea, from horrifying cyborg midwives to crazed splicers. Hell, it can even freeze people if you wanted it to. That's how magical of a weapon it is.

I never one hit the Vyrelords... Vyrewatches, maybe. Normal vampyres, definably. But not the Vyrelords.

I'm a big Halo fan and I've NEVER gotten de' Scarab Gun. I tried but never succeeded.