Twi would have to be hypertensive. And Pinkie Pie too much sugar, type II diabetes. Or maybe ADHD … And Applejack would have some kind of RSI from bucking too many trees. And Rainbow Dash would either have concussions, or perhaps altitude sickness from flying too high. And Fluttershy, probably agoraphobia. And Rarity, I don’t know about Rarity … maybe she’d swallow a pin.
I would not at all be surprised to see Twilight Sparkle’s blood pressure off the charts. (Assuming Equestria uses the traditional sphygmomanometer, I’d expect the mercury to break through the top of the column, and maybe through the top of the tree that houses the library.)
I am less worried about Pinkie, despite her eating habits, since she seems to have a linear accelerator built into her metabolism. I fully expect her to keep a supply of Higgs bosons scattered around town in case of emergency.
Fanon has it that pegasi generally end up with lots of broken bones for pretty much the obvious reason. In a short story I wrote, Rainbow Dash is done in by pneumonia, a disease that seems to be more common among weather specialists, perhaps due to extended exposure to aerosols. And I’m thinking that sooner or later, Fluttershy is going to catch something from one of those motley critters she watches over at the edge of the Everfree.
RSI seems plausible for Applejack, though I suspect the entire Apple family has relatively high resistance to that sort of thing. As for Rarity, I see her as borderline bipolar, or maybe a bit over the line, given the contrast between her manifest joy in completing a task perfectly and her horror at the various and sundry events that qualify as the Worst Possible Thing. Not that swallowing a pin is anything to be joyous about.
(Picture: Pinkie Pie after a bad batch of muffins in “Applebuck Season,” from the first season of MLP:FiM.)