A Half-Life Source sequel. Half-Life 2: Source 2.
Jetforce Gemini reboot
Deus Ex HR has a sequel. It’s called Deus Ex.
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Insert obligatory System Shock suggestion.
HR2 is set 25 years before the original. There’s plenty of room for a direct sequel. But nice try
^^^THIS!!!^^^
Descent 2
Plants vs. Zombies 2 has already been confirmed.
YEEEESSSS!
This! And the older ones should frigging drop in prices…
The latter needs a remake!
Tales of Vesperia needs a direct sequel and it would also be awesome for it to come out in English for the PS3. Sigh.
Age of Empires Online is not bad (released last year sometime as I recall), I’ve been playing that a bit every now and then. That said, I’ve enjoyed every Age of Empires game. None of them have been as awesome as AOE2 was, though. I never have/will get the same replay value out of any game as I did for AOE2.
Star Wars Battlefront & Republic Commando, Age of Empires, Rollercoaster Tycoon, Predator Concrete Jungle & Rise of Nations
S.T.A.L.K.E.R…Someone must do it. 
Severance: Blade of Darkness really needs a sequel.
StarWars Battlefront 3
StarWars Republic Commando 2.
StarWars KoToR 3.
StarWars Pod Racing 3D.
Vampire: The Masquerade: Bloodlines 2
Half-Life Opposing Force 2
Deus Ex: Human Evolution.
Evil Genius 2
World In Conflict 2: Red Guard.
Startopia 2.
Defcon 2.
Act of War 2.
I WOULD FORGO EVERY ONE OF THESE GAMES IN EXCHANGE FOR DEVELOPMENT OF
StarWars: Jedi Academy 2.
Psychonauts 2.
A new Oddworld game (instead of just re-releasing their previous ones in HD).
Streets of Rage 4.
A new Jedi Knight game.
Proper Crysis sequel.
With the release of Black Mesa, we need a sequel to it; Black Mesa 2!
Bethesda 
.
I forgot about this. My favorite Rare game by far, and one of my favorite N64 games.
Day of Defeat
Heretic (I wanted this most)
Mirror’s Edge
People keep mentioning Age of Empires, I say Age of Mythology.