Like in this picture:
Because of their orientation to blow air upwards the fan blade and its motor hang down from the fan housing and this can cause stress on the fan. Over time it comes loose and may start making weird sounds.
Which is what has occurred on my system. One of the four fans in the top is now making this really annoying rattling. I've ordered a replacement fan which is coming tomorrow. Thanks Amazon!
I made this thread just to illustrate the problem of running fans for a long time upside down. They work best when on their side or when blowing down. So if you're building a system and don't want to replace fans every year like it seems I'm going to do you can always flip them the other way round and use the top as an intake.