I usually get this question when I talk to someone about PPV campaigns. It's a tough question to answer because it somewhat depends on your budget. It also depends on how much traffic volume the sites you are targeting have.
If you are targeting really high traffic sites, you would obviously want to start smaller..maybe 10-50. If you are doing targets with not much traffic volume you will need a lot…more like 100+. Now, having said that…the people really driving serious volume are using thousands of targets. Don't start out this way though! I would recommend starting out with a small mix of low, medium, and high traffic targets and scaling from there.
Think it's going to be too hard coming up with thousands of URL's to target? Well, it is if you're not thinking the right way about it. Say you are targeting a scholarship campaign; instead of just coming up with a list of scholarship sites, you really need to be thinking more about the type of people visit those sites and what OTHER types of sites they visit. This should give you enough to think about for now but I will post more on this subject.