2001 Ford Ranger #41 Fuse
 

#41 Fuse keeps blowing causing motor run like crap. Check O@ sensors and wires running, no issue, Unplug transsmission motor runs better but trans O/D light is now on (unplugged). Any one have any ideas as to what I should do next?

From what I could find fuse 41 protects the oxygen sensor heater circuit. That circuit is fed from the ign switch. Suggest you unplug o2 sensor and physically check the entire wiring from the fuse panel back to the o2 sensor. For it to blow a 20 amp fuse quickly , it has to be rubbing on either sheet metal or some metal where the wire has rubbed through and now is providing a direct short to ground. Sometimes engine movement when starting off allows the engine to move enough to stress wiring harnesses and eventually the wires will rub through and find an unintended path to ground.