I think I know the answer to this, but I will ask anyway.

So I have my 440 in my GTX and wanted to get the motor running, so I ran the fuel line from the tank to the fuel pump, then pump to the carb. The return line was left open (this was a temporary thing).

I am unable to keep fuel pressure to the carb and I am thinking that this is due to the return line left open. Does this make sense or am I way off?

Also, does everyone run with the fuel vapor separator or have you removed it?

What do you mean return line left open? Isn't it pouring fuel if you don't have it hooked up? You can run it with the vapor seperator disabled by putting a hose clamp on the rubber part of the vapor return hose.