There are so many answers to this, but none of them really feel right or true.
His hatred for the Kryptonians was justifiable and his insatiable desire to research and destroy them made sense. The fact that it made him a little if not a lot crazy that no one else but him really seemed to care that Smallville was casualty central, that makes sense too. Even the slow but sure continual ingestion of green kryptonite, eating away at his mental state, that's reasonable.
But really, none of that explains his hatred for Superman. He knew Clark personally and knew he wasn't the kind of person to ever become like the other Kryptonians. Even if Lex took precautionary measures, in the event Clark did become evil, he had no need to fear him and he knew that.
As for his "breakup" with Clark as a friend - that comes down almost entirely to him wanting to hook up with Lana. Clark and Lana were going through a rough patch, and Lex took advantage because Lana was on his side about all the weirdness in Smallville and actually egged him on in his pursuit of information to destroy the Kryptonians.
It has almost nothing to do with Clark personally. The whole 'but tell me your secret' bs was just icing. The cake of the story is the writers wanting Lana in the story line no matter what, so they killed the Lex/Clark friendship to make it so. I'm in the middle of re-watching for like the third or fourth time, and I still find myself yelling "but why?" at my TV when Lex and Clark argue about nothing - it's all because Lex wants to be with Lana, and there's no real way to justify going after his best friend's ex. I guess this was the big signal that Lex was 'truly bad' but him pursuing a good friend's ex is a shit way to do that.
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