In no particular order
babble-fish (HHG2G)
portal gun (portal)
The BFG9000 (DOOM)
A Working model of the Skasis Paradigm (5 shiny points to whoever knows where this is from)
The Homosapien propulsifier (capable of firing men, and Grifs!)
Chopper (It has Cannons and can smash anything, plus it looks freaking sweet in screenshots as it dives off a jump)
---Fallout 3---
T51B power armour (Because the smart wastlander knows how to dress for deathclaw encounters)
railway rifle (It's a gun that pins body parts to walls, need I say anymore)
MIRV (No job too big or too small that this bad boy can't vapourise)
Tesla cannon (Serious win at the cost of 1 ammo per shot)
Chinese stealth armour
Gauss rifle (mainly the sound as it splits a muties head in 3)
Auto-Axe (Goes from 0 to gibbage in 2.6 seconds)
Deathclaw control scrambler (Because setting pets on their owners is always hilarious)
PIP-BOY 3000