I would have to say that competing with ndemandaffiliates.com is going to be your biggest challenge. They got every superduper affiliate on lockdown, using the latest super secret HasOffers software. You've got quite an uphill battle chief.
Most networks have a mash up of the same offers. You can only push payouts so high before there is no margin left.
I'm a fan of networks that specialize in niche offers and don't just send you a mass email that says "these offers are killing it"...not all traffic kills it on the same offers.
Somehow I think Wickedfire gets creepier every day...
I think biggest part is the legal planning in advance. Nothing cuts profit harder than taxes and legal fees... but setting up a company in a foreign country can be quite hard if you are a stupid American.