He'd have cast Jensen Ackles as Clark. We know that for a fact.

The Smallville producers loss was Kripke's gain.
In all seriousness, Kripke would have had a general outline and plan for the series, something that Smallville lacks. Kripke wouldn't sign on for nine seasons. The biggest difference is that he'd have encouraged
much more of an emphasis on the Clark/Lex relationship and its eventual disintegration than on the never ending romantic Clark/Lana relationship. When the young actress they'd intended as Dean's love interest during season two didn't click, she was written out the same season. The love interest's mother actually became more popular; the SPN writers incorporated her more. Momma is back this season. Kripke and his writers script several wickedly lurid references to Dean's one night stands; I don't know if that would have worked for white bread Clark but Kripke would have tried to make Clark a bit more caustic than he is. When future Dean asked present Dean for a bit of information only he would know and Dean answered that one of his girlfriends had made him try on her pink panties and he liked it, well.....I just don't know if the Superman franchise folk would have allowed that.
Who can say when Kripke would have wanted Jonathan Kent to die, but he'd have made it count. The episode where daddy Winchester died remains the most poignant episode of Supernatural to date. EK wouldn't have made it all about saving a girl, that's for sure. It was all about daddy W making a deal for Dean, which ultimately led to Dean's self esteem being so low that he bargained away his own life for his brother's. In Supernatural land, actions have repercussions that last. People remember what they did an episode ago, a month ago, and a year ago.
I don't know how much gore Kripke could have gotten away with in Supernatural.

Different universe there, but Clark would have been more interesting.