Assuming you can break away from Diablo III and Max Payne 3, there are plenty of deals to be had this weekend, including steep discounts on Darksiders, Syndicate, The Darkness II, both recent Batman games, Mafia II, Left 4 Dead 2, Just Cause 2, Sanctum, Mirror's Edge, SimCity 4, the first three Assassin's Creed titles, Far Cry one and two, as well as virtually everything in Paradox Interactive's arsenal. Also of note, the Humble Indie Bundle has added three more titles (Lone Survivor, Braid and Super Meat Boy) to what was already an awesome bargain.

Steam
78 Magicka Collection $6.24 (75% off)
76 Hearts of Iron 3 Collection $14.99 (50% off)
Penumbra Collector Pack $9.99 (50% off)
75 Cities in Motion Collection $19.99 (50% off)
75 Majesty 2 Collection $9.99 (50% off)
84 The Lord of the Rings Online Steam Starter Pack $14.99 (50% off)
65 King Arthur Collection $24.99 (50% off)
84 Crusader Kings II Collection $24.99 (50% off)
82 Mount & Blade Collection $17.49 (50% off)
74 Warlock - Master of the Arcane $9.99 (50% off)
The Kings' Crusade Collection $9.99 (50% off)
Crusader Kings Complete $4.99 (50% off)
Hearts of Iron 2 Complete $7.49 (50% off)
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Amazon Digital
91 NBA 2K12 $9.99 (50% off)
75 Medal of Honor $15.00 (25% off)
85 Rift $5.58 (72% off)
82 Tropico 3 $4.41 (56% off)
78  Tropico 4 $19.99 (50% off)
SimCity 4 Deluxe Edition $14.77 (26% off)
Crysis Maximum Edition $8.99 (70% off)
Major League Baseball 2K12 $9.99 (67% off)
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GameStop
82 Darksiders $4.99 (75% off)
76 Assassin's Creed $4.99 (75% off)
89 Assassin's Creed 2 $9.99 (50% off)
88 Assassin's Creed: Brotherhood $14.99 (50% off)
70 Homefront $9.99 (50% off)
88  Battlefield 3 $39.99 (33% off)
Far Cry Bundle $4.99 (75% off)
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GamersGate
74 Syndicate $20.40 (66% off)
81 Chronicles of Riddick Assault on Dark Athena $3.74 (75% off)
79  Mirror's Edge $6.78 (66% off)
74 Sengoku $4.50 (50% off)
82 Just Cause 2 $5.98 (60% off)
82 Just Cause 2 Complete Edition $10.00 (60% off)
Renegade Ops $6.00 (70% off)
74 Sanctum Collection $6.80 (66% off)
79 Lead and Gold: Gangs of the Wild West $1.50 (50% off)
Just Cause $5.20 (60% off)
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GameFly
77 The Darkness II $12.49 (75% off)
92 Batman: Arkham City $7.49 (75% off)
90 Batman: Arkham Asylum GotY $4.99 (75% off)
78 Prototype $4.99 (75% off) 
81 Mafia II $7.49 (75% off)
89 Left 4 Dead 2 $6.79 (66% off)
89 Call of Duty: Modern Warfare 2 $9.99 (50% off)
SimCity 4 Deluxe Edition $4.99 (75% off)
Grand Theft Auto IV $4.99 (75% off)
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Green Man Gaming
71 Nuclear Dawn $12.47 (50% off)
62 Jagged Alliance: Back in Action $19.99 (50% off)
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GOG
50% off Anuman titles