Either be an invite-only program, or don't (approve instantly).
Any professional affiliate with the intent to fraud you is going to get approved through your manual process 9.9 times out of 10. It's not like you're getting a sample of their DNA to compare to a "Fraud Bank".
You WILL be losing potential legit affiliates by having a manual approval process; it doesn't matter if it takes minutes, or a few days (or more as I've seen some in the past who take a week to approve you). If the affiliate looking to use you, cannot plug you in right away, he probably turns to someone else.
As for porn surfers signing up and "seeing your millions of dollars worth of promo content" (quoting someone above), that shouldn't concern you; plenty of other ways they can go about seeing your content if that's what they are after.
Post-signup, once/if traffic/sales start coming in, that's where you should be screening for fraud. Activity patterns, billing patterns, CBs/returns (granted takes time to notice that one), sign ups from pre-paid cards (identified by BIN number DB), etc... should all be automated generating flags and alerts for you for deeper manual investigation.
Before first payment is issued, you can also "verify" the account by IM or telephone, etc...
Accounts who sign up and are inactive for X period of time, you can simply shut down. I've heard people say they don't like "bloating their DB", if you don't have a DB that can handle a few hundred thousand rows, active or not, you have bigger problems to worry about
