I have spoken to a few different affiliates and have found that some guys say S2S is better and some that say iFrame Pixels are more accurate.
What is the real difference?
I would say S2S is more accurate, but let someone more techie chime-in.
S2S is more accurate than C2S (iframe/image pixels). S2S will track 99% of all conversions whereas iframe/image pixels will be more around 90-95% so if you can choose, always go for S2S
There are so many reasons that would cause an iframe/image to not load or work. Some of the more problematic being adblockers, or cookie wiping
In general as long as your server is online an S2S will work.
I tell people to setup both if possible. Because iframes allow for loading piggyback pixels which can be very beneficial for optimizing by passing conversion data back to your traffic source or setting burn pixels for remarketing etc.
Its also not always (its not in most cases) up to you as most advertisers will only work with S2S.