I’ve had the exact same issue that you’ve had with USB printing. I first noticed it when using my octopi setup and then continued to notice it with connecting directly to my computer. Prints would start just fine and after a few hours, or even a few minutes, they would sometimes just fail. The print head would stop moving, the temperature would hold steady, and everything would just stop. Then, sometimes it would run a 20 hour print just fine. It turns out that the problem was an interruption in the USB connection. I’m still not sure if it’s just a bad cable or bad port on the printer.
My solution so far has been to just slice in Cura, save to a SD card, and print from the SD. I’ve now gone through multiple 20+ hour prints with no issue when I used to have failures fairly frequently.
Also, I’ve found simplify3d to be kind of hit or miss for me with leaving random holes in models. Not sure if it’s the model, the program, or user error. It’s great for some things, but I generally rely on Cura.