One reason is overheating. I don't know how powerful does a fan have to be to compensate for the lack of moving through the air. Built-in fans hardly even help (and not every treadmill has them). And directing a separate fan right at you doesn't reduce sweating as much. Don't you notice the sweating yourself? I'm completely drenched 30-40 minutes in even if I run easy. It's like running outside in 90+ degrees with high humidity. Luckily (usually) no direct sunlight on treadmills, or they would have been deadly.
The other thing is motor power and energy return of the treadmill surface. These two are connected. When your foot hits the treadmill, it works against the motor. If the motor is like 10 hp, it would barely notice and will keep rotating the band smoothly. Weaker 2-3 hp would struggle and work very uneven. This makes it harder for you to run. And the qualities of the surface can either return more impact energy back to your spring, or dissipate it into heat and the fight against the motor.
Normally I also have a hard time running on treadmill, but once I had access to a somewhat luxurious gym on a long business trip and they had some powerful expensive treadmills. It was winter and I could open a window next to the treadmill, outside was below freezing. I was able to run 10K time trials close to my road PR as my weekly tempos there. Something I don't really have the guts to do on the road. And it was not some deceptive speed setting, I used a footpod to verify.