I'll do a Top 5 for male and female protagonists. No particular order for each.
EDIT: kunonabi inspired me to add the game(s) where each protagonist appeared.
Male
Phoenix Wright - Ace Attorney (Phoenix Wright) series
Duke Nukem - Duke Nukem series (but especially 3D)
Doomguy - DOOM series
Leon S. Kennedy - Resident Evil 2, 4, 6 (but especially 4)
Solid Snake - Metal Gear (Solid) series (but especially MGS1 and 2)
Female
Aya Brea - Parasite Eve series
Terra Branford - Final Fantasy VI
Ada Wong - Resident Evil 2, 4, 6 (but especially 4)
Jill Valentine - Resident Evil 1, 3
Lara Croft - Tomb Raider series