Harvest Moon protagonist. Like Mario the design is simple, yet instantly recognisable.
Also, the HM cow is a psuedo mascot for the game, and I love this design.
George Stobbart from Broken Sword. A simple everyman, yet again, is instantly recognisable as the face of the series. A lot of character designs are defined by what they wear, but for George it's all in the face and hair.
Hildegard von Krone, Soul Calibre. Dat armour!
John Marsden, Red Dead Redemption. Such a bad-arse. You knew he had a rough, shady past within seconds of seeing his face.
Shepard, Mass Effect. This is all about the N7 armour, which remarkably managed to make both John
and Jane recognisable.
Morrigan - Dragon Age. I really liked the concept art for the character, but felt the in-game implementation did a really poor job of reflecting the original design. Also the voice (whilst I love Claudia Black) really didn't suit this design IMO.
Iota from Tearaway. Adorable, I love this guy. Almost every character/creature in Tearaway is wonderfully designed.
Max - Sam & Max. Something I really admire in character design is when personality is conveyed visually. Take one look at Max and you can instantly tell he's an utter psychopath.