what do you consider to be major bosses?

I agree with this. 5mins of kimera hunting got me about 16mil profit. As for the actual challenges, Bigfoot and Anego.

Anego? What about lady boss is remotely hard?

Semi off-topic:
However It's one of the worst bosses released because it is the biggest source for problems and drama in the high lvl community. Some children actually camp there and claim every channel as their own. They ks, bring armies of cronies, all in the name of exp and "power".
Last time I thought I'd amuse myself with killing one, A guy showed up. He sat there for 10 minutes, and then starts to attack. Soon a lvl 200 hacker NL in the same guild pops up with both SE and HS mules and joins his pal in the ksing. I got the most exp, so why did they even bother? Oh yea, some people get off on ruining others fun...

Reduce the exp of the open map bosses so that they are good for hunting drops, doing quests and give a little % on your bar, not something that attracts the scum and dirt of each server.