Google Checkout $20 off $50 for me, without question. The timing was great (made Christmas shopping a breeze), it didn't rely on a glitch, it didn't need a code, it applied to any item in stock, and it had unlimited uses. Any deal that makes you blow off the DDD 20% off is a major one in my book.
I see a lot of votes for TRU clearance, but I found that one to be pretty disappointing, since the one from last year set the bar so high. That one was just epic... the deals for RE4 cube, Pikmin 2, Fatal Frame II, Doom 3, etc. really seemed too good to be true at the time.