The major obstacle to flying extremly long Predator sorties is reliability. But that has been rapidly improving over the last decade. Combat aircraft in general are becoming more reliable, even as they become more complex. For example, in the early 1950s, the F-89 fighter had 383 accidents per 100,000 flying hours. A decade later the rate was in the 20s for a new generation of aircraft. At the time, the F-4, which served into the 1990s, had a rate of under five per 100,000 hours. American F-16s and F-15s have loss rates of under 4 per 100,000 hours.
Combat aircraft have gotten more reliable and easier to maintain, despite growing complexity, for the same reason automobiles have. Better engineering and more sensors built into the equipment makes it easier for the user and maintenance personnel to detect potential problems. Aircraft used the computerized maintenance systems, currently common on new aircraft, long before automobiles got them. Unless you have a much older car that still runs, or a real good memory, you don't notice the enormous increase in automobile reliability. But older pilots remember because such changes are a matter of life and death if you make your living flying an aircraft. And commanders know that safer aircraft give them more aircraft to use in combat and more aircraft that can survive combat damage and keep fighting.
Unmanned aircraft have, until quite recently, had a much higher accident rate, which is largely the result of not having a pilot on board and the software and hardware not benefitting from decades of improvements to remedy that. The RQ-1 Predator had an accident rate of about 30 per 100,000 hours four years ago. Older model UAVs had much higher rates (up to 363 for the RQ-2A). This year, the Predator accident rate is lower than the F-16s, largely because of better flight control software and more reliable UAV components.