Liquid Snake
A clone of legendary hero Big Boss and thus Snake's genetic twin, Liquid is the man behind the whole Shadow Moses operation or, at least, the man who thinks he is. Cold-hearted and manipulative, Liquid's evil is born of jealousy and anger towards Snake. Believing his body to be the recipient of Big Boss' recessive genes (necessary to give Snake all the good ones before birth), Liquid hopes to take control of Metal Gear REX and offer it to the highest bidder. After failing to destroy Snake using the bipedal battle tank, Liquid and his brother settle things with fisticuffs and, finally, a high-speed chase.

Special abilities: Snake's sibling is capable of devising insidious plans, piloting both a Hind helicopter and Metal Gear, impersonating Snake's mentor, Master Miller, and sounding like a very posh Leonardo from Teenage Mutant Ninja Turtles.
Weaknesses: Liquid will often put his anger and tendency to deliver expository speeches well before self-preservation. Oh, Foxdie also does him in.
Trivia: Liquid lives on in Metal Gear Solid 2: Sons of Liberty, kept within arm's length of Revolver Ocelot.

Young Ocelot
Metal Gear Solid 3's 1960s setting brings with it a young, impetuous and overconfident Ocelot. He has a lot to learn about battle, and Naked Snake (who eventually becomes Big Boss in this time period) is just the one to teach him. Their first encounter leaves Ocelot unconscious and his pride in ruins, but not before Snake dispenses some life-changing advice: Try using a revolver instead of a semi-automatic, dude! Though bested by Snake several times following their initial meeting, Ocelot eventually grows to respect his adversary.

Special abilities: The arrogant sharpshooter has a particularly nerve-wracking variant of Russian roulette, with a bullet placed in the chamber of one of three juggled guns. He's also able to summon his battalion of soldiers by, err, emitting a loud and utterly bizarre meow.
Weaknesses: Arrogance is Ocelot's downfall. Arrogance, and beehives.
Trivia: Though it would save the good guys a lot of trouble in the future, killing an unconscious Ocelot ends the game and, more importantly, creates a TIME PARADOX.

Rosemary
Undoubtedly Metal Gear Solid 2's most annoying obstacle, Rosemary attempts to thwart and confuse players whenever they try to save the game. Strange emotional outbursts, meaningless questions and completely inappropriate sentimentality all need to be conquered before attention can be returned to the mission. You can almost hear Raiden's sigh of relief when his cloying girlfriend is replaced by a bonkers computer AI towards the end of the game.

Special abilities: Rosemary attacks with unpredictable mood swings, rampant paranoia, accusatory trap questions and reminders of irrelevant anniversaries. And she's not even married yet!
Weaknesses: She's powerless against gratuitous use of the skip button.
Trivia: No more questions. We have Rosemary.