* Hosting costs. Reddit was very lucky to have imgur pick up a lot of its bandwidth in its early days, but free image/video hosting sites are cyclical: absent a benevolent billionaire, the costs will rise with popularity, and the site will eventually need a source of revenue, which will introduce friction and start its inevitable decline in popularity.
* Moderation. Always a highwire tightrope act. Most Reddit spin-offs of the past several years have been focused on minimizing moderation, which ends up attracting people who tend to get banned from other places before the site gets a chance to form its own identity and pick up steam.
* Network effects, which are basically a lottery. You can have a scalable service with great UI, and a solid moderation story, but you still need to get lucky and catch lightning in a bottle to take off. This is common knowledge, which makes it even harder to justify starting to develop or use a new social medium.
Personally, I like places like HN, which focus on good moderation without trying to scale up. We are blessed to have dang, but if the site were structured more like Reddit or a forum with different boards, I bet it would become unmanageable very quickly.