Heat-Seeking Bullets - In the 1984 Tom Selleck film Runaway bullets could be calibrated to individual heat signatures. The bullets would go around people and corners to seek out the target, not unlike the cartoon bullets from Who Framed Roger Rabbit (but a bit brighter)? Despite being highly, highly effective, there are two problems that place these bullets at the bottom of the list. First, any physics professor would have a heart attack espousing the problems with actually creating a working model. Second, all the great sniper movies like Enemy at the Gates would be rendered moot, and the author loves sniper films.
Lasers - Has any weapon been so popular as the laser in science fiction? The laser has aged well considering James Bond was outmaneuvering them back in the sixties. Lasers have yet to be turned into a usable weapon despite Val Kilmer's best efforts in the 1980's. However, their pretty colors and popularity at planetariums everywhere for Pink Floyd tributes has us hoping they will someday reach a point where they become economically and physically feasible for warfare. Until then, pass me the stuff, man. Wait, what was I just talking about? Oh, wow man, look at the colors!
The Holy Hand Grenade of Antioch - And the Lord spake, saying, "First shalt thou take out the Holy Pin. Then shalt thou count to three; no more, no less. Three shall be the number thou shalt count, and the number of the counting shall be three. Four shalt thou not count. Neither count thou two, excepting that thou then proceed to three. Five is right out. Once the number three, being the third number, be reached, then lobbest thou thy Holy Hand Grenade of Antioch towards thy foe, who, being naughty in my sight, shall snuff it." Amen.
Biochemical - Technically, biological and chemical are two separate categories of weaponry. But who cares? They are tremendously effective at devastating the opponents' forces, both physically as well as for morale. Unfortunately, biochemical weapons have a nasty habit of, well, backfiring. A shift in the winds or a misfire, and both you and your enemy have lost the skirmish. Still, very efficient and cheap, making it a top pick for desperate countries faced with an overwhelming opposition.
Portal Gun - Certainly there have been any number of creative weapons in video games. Ice guns, trip beam explosives, shrink rays, flak cannons, the gravity gun, the nailgun and shock beam rifle come to mind. None have been as creatively implemented as the Portal Gun. There is something satisfying about a gun that can be used to both defeat the enemy and get you where you need to go. If it were somehow possible to use in reality, there would be all sorts of special operations missions possible. All you would need is a single Navy Seal and the Portal Gun and you could pretty much depose any hostile government in the world. The best part is that you could do it without making it look like anyone was ever even there. Imagine the headline, "Mahmoud Ahmadinejad, his entire cabinet, and his personal guard were all found dead today, having seemingly leaped to their deaths from the top of the government building."
Prostitutes - You thought women only recently entered the armed services? Diseases killed twice as many soldiers during the Civil War as died from battle. There were more cases of venereal diseases than of measles, mumps and tonsillitis together (Source). One estimate puts it, "one-third of the men who died in Union and Confederate veterans' homes were killed by the late stages of venereal disease (source)." Despite this being probably the best entry for something humorous, I am at a loss.
The Force - The author refers not just to the Force, but to the use of telekinetics of any sort at any time in fiction. When Darth Vader crushes the neck of an officer, it's box-office gold. Unlike some of the other weaponry, like lasers and biochemical weapons, telekinesis would be just as useful outside of combat. Lost your remote control? No reason to buy a new one. Need an extra roll of toilet paper? No problem. Someone about to get struck by a car? No need to put yourself in danger. Move other objects and yourself! Take a flight anywhere you'd like for free (just don't fall asleep). While you're there, try not to get assassinated by evil ninjas from a rogue shadow organization, though.
ICBM (Inter-Continental Ballistic Missile) - The ICBM changed the world overnight. The ability to strike any enemy from any distance practically ensured that nobody would ever attack anyone else, lest they usher in the apocalypse. It's kind of like if you gave every man woman and child worldwide a handgun. Wait a minute...
Atomic - Nuclear weaponry has pure staying power. It is still the most effective, destructive weapon ever created, capable of annihilating our entire species. Take that holy hand grenade! Then again, it's also a bit like trying to dial the telephone while wearing an oven mitt: you can't help but hit every key. Plus, that pesky nuclear fallout and long-term environment damage kind of ruin any plans for invasion because it just kills property values.
Fire - Deadly, useful, and occasionally the avatar of God (Deuteronomy 4:12), fire is the Swiss army knife of weapons. Feared on land, sea, or in the air, capable of leveling cities, and difficult to control, fire is what makes it possible for most of the other weapons to work. It can be as destructive as a nuclear weapon when used tactfully and dispose of the bodies, or cook you dinner and heat your home. Can the Force make me dinner? Yeah, I thought not.
Honorable Mentions
Chainsaw - Chainsaws are always great for a gorefest, but are particularly cool when worn in place of a hand. Remind me again why Mega Man never had a chainsaw option?
Claws (preferably adamantium)
Fists - The ultraportable, undetectable weapon that's always there as a last resort.
Rail Gun - If you've ever seen Eraser, you'll realize that the rail gun is a very cool weapon, but purely for its smoke effect.
M16 rifle with M203 grenade launcher
V-MADS (Vehicle-Mounted Active Denial System) - This is certainly the best thing to ever happen to modern weaponry, though it is still being developed. The 95-GHz energy penetrates 1/64 inch into the skin and produces an intense burning sensation. The technology is an incredibly effective crowd-control system. It also makes for great parties at local fraternities. "Dude, I'll bet you can't stand in the beam for longer than me." "Can to." "Alright, let's do it then." (in unison) "AAAAAAHHHH!"
Shotgun - Otherwise known as the Boomstick
Gravity Gun - Telekinesis, but with a gun. Sorry, but the telekinesis is much cooler, and will always get through airport security.
Swords - Swords seemed really cool until writing the list, then they just seemed kind of quaint.
Death Star - Yes, one of the coolest and most awe-inspiring weapons, for sure, but also incredibly inefficient and, well, impossible. What's that? Something about the list and the Force and the Portal gun? I'm sorry, but I can't understand you when you mumble. Let's move on.
Lifetime achievement award
The Terminator 800 unit is not a weapon specifically, but its ability to learn, ingenuity, and stamina make it one hot piece of hardware. Since it cannot be wielded, it had to be excluded, but it is an awesome piece of machinery.