Although Steam's holiday event has expired, the service has a 50% debut discount on Age of Empires III (Microsoft seems to be gradually pushing its titles on Valve's platform). If you're still hunting for mega sales, GameStop and GamersGate have deals on some top titles, including Dead Space 2, Mafia II, Red Faction: Armageddon, The Witcher 2 and Super Meat Boy. It's also worth noting that Indie Royale has a New Year Bundle with Nuclear Dawn and three other titles available for about $4.

Steam
Age of Empires III Complete $19.99 (50% off)
Lead and Gold: Gangs of the Wild West $4.99 (50% off)
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GameStop
87 Dead Space $9.99 (50% off)
89 Dead Space 2 $9.99 (50% off)
82 Mafia II $7.49 (75% off)
78 Tropico 4 $19.99 (50% off) 
81 Tropico 3 $9.99 (50% off)
71 Red Faction: Armageddon $14.99 (50% off)
68 Need for Speed: The Run $39.99 (20% off)
Zeit2 $4.99 (50% off)
44 Stronghold 3 $39.99 (20% off)
85 FIFA 2011 $19.99 (33% off)
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GamersGate
79 King Arthur Collection $10.18 (66% off)
75 Two Worlds II GotY $24.98 (50% off)
86 Machinarium $4.98 (50% off)
75 Dead Island Four Pack $89.85 (55% off) 
83 Orcs Must Die! $7.50 (50% off)
66 Dungeons Mega Pack $16.48 (50% off)
60 Sniper: Ghost Warrior Gold Edition $11.98 (60% off)
90 The Witcher 2: Assassins of Kings $19.98 (50% off)
85 Super Meat Boy $3.73 (75% off)
Neverwinter Nights Diamond $4.98 (50% off)
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Direct2Drive
70 Homefront $7.50 (75% off)