In my (admittedly limited) experience, the main reason founders refuse acquisition offers is because they believe their startup has a great future and will be worth a lot more later. I don't think the thought process is ever, "Well, $50 million is great, but you know what? We're enjoying what we do so much that we'll turn it down even though that's the most we will realistically be able to get."
Or even more simply, their investors offer to let them to cash out a few million worth of shares as idiot insurance. This still doesn't really explain why a 22 year old Mark Zuckerberg had the cojones to turn down $1 billion. Very few people in the world would have done that.
