Arc Fatigue: Even the story's fans are starting to wonder exactly when the story is going to end. Project Horizons is now longer than the original story, with no ending in sight.
This is averted after the Thunderhead arc beginning in chapter 58. Many of the big mysteries are starting to be answered. Word of God has assured readers the ending's in sight. And as of chapter 70, Somber looks to be delivering on that promise as the climax looks to be going off at any moment.
And as of August 29, 2015, the story finally wrapped up at just above 1.7 million words.
Awesomeness Withdrawal: If you've stuck with the story to its end, and been folowing for years as many of the readership have, then seeing the epilogue is quite a Tear Jerker indeed. After 2000 pages of character development and trying events, it's finally time to say goodbye.
Base-Breaking Character: Goldenblood. While some readers agree with the author's intentions that the character should explain the state of wartime Equestria, others feel that he lessens the original characters and events by stealing away the responsibility for their actions.
On a meta level, the story itself. Love it? Hate it? Indifferent? Either way, just mentioning Project Horizons is grounds for a Flame War in some circles. Doesn't help BJ and Pip tend to get compared with each other a lot.
Darkness-Induced Audience Apathy: All but the most die-hard readers eventually lose interest after being continuously shown how absurdly the story's setting sucks. We've long since reached the point where canon Fallout - no, scratch that, Van Buren Fallout - is a less depressing world.
Boo, the allegedly soulless clone that Blackjack befriends in Hippocratic Research, recieved fan art and an independent Character Blog within days of her first appearance.
Charity, a surprisingly shrewd merchant filly. She's both cute and amusingly greedy, practical, and still young enough to be a Crusader. Yet nevertheless so dependable and fair as to earn most of the Hoof's respect regardless.
The reason why Stable 99's recycler wasn't able to get rid of the Raider Virus? It's based on Creutzfeldt–Jakob disease and Mad Cow Disease which are caused by prions. Prions are proteins that act like viruses but cannot be destroyed short of destroying the material that they are contained in.
The reasons for Glory's mother becoming a dashite aren't really explored, save for the fact that she was originally from the surface and therefore unpopular with the Enclave. Then you consider that Glory mentions having four sisters, the youngest being a pair of twins. The Enclave has strict limits on breeding due to population and resource concerns - as a mother of five, as well as an outsider, it's no wonder that Dawn caught a lot of flak. Her husband's rank and political influence were probably the only things keeping her from being banished (or worse) sooner.
P-21 served as a breeding stallion in Stable 99 for over ten years. It's unlikely that Scotch Tape was his only child. And if he did have any other children, Blackjack killed them all in the massacre of 99.
Goliath, the enormous train-pulling pony that Blackjack and friends meet at the beginning of Chapter 36, is mentioned to have gotten his incredible size from an encounter with Killing Joke. BJ notices a grievous scar on Goliath's mother's belly, and suspects that the injury was caused by a landmine. She fails to consider another, somewhat darker possibility.
Every single pony that has died in Hoofington, including those that Blackjack and company have killed, has had their soul sucked into the swirling vortex of endless torment and despair that orbits around the fallen star that lies at Hoofington's core. Every single one. Count them.