Pickit 3 and PIC18F46J53
These are some things to check:


Truly make sure all connections to the PIC and pickit3 are correct, triple check if need be
Test pickit3 + cable set up against a known working board if possible
Try different USB cables, I have had some flaky red cables come with pickit3s in the past
Verify that the PIC is being powered properly
If you are using the pickit3 to power the PCB, make sure it can provide enough current
Use the pickit3 software and not MPLAB IDE/X (http://ww1.microchip.com/downloads/en/DeviceDoc/PICkit3%20Programmer%20Application%20v3.10.zip)

Using the above tool, you can put the programmer in "slow mode" to allow for PCB layouts that have loads on the programming pins
If you are using the pickit3 to power the PCB, you can also adjust the voltage to help with pin loading issues



I have little experience with MPLAB X, but it doesn't seem to easily bring out the functions that the standalone software provides.