Each member of the 411 staff discusses their top 5 video game sequels of all-time! (Fallout 3, Marvel Ultimate Alliance 2, Mass Effect 2, PC, PS3, Silent Hill 2, Street Fighter 2, Uncharted 2: Among Thieves, Wii, Xbox 360)
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Which makes the wait for the next one so painful.
2. Portal 2
3. Team Fortress 2
No seriously, the original games came out so long before the sequels that the sequels end up being way different and better games.
Left 4 Dead 2 Though? Nope.
Edit: It's actually a prequel, but it's so good I'll leave it here anyway.