On the first playthrough? The easiest mode. There's nothing more that will take away your passion for a game, than a game that keeps kicking the stuffing out of you. On my following turns, I always choose the hardest mode.
Very Easy - "Like a smooth, gentle breeze"
Easy - "Like a pleasant, warm draft"
Medium - "Like a stiff gust of wind"
Hard - "Like a strong, fierce gale"
Very Hard - "It's a bloody tornado"
On the first playthrough? The easiest mode. There's nothing more that will take away your passion for a game, than a game that keeps kicking the stuffing out of you. On my following turns, I always choose the hardest mode.