From I-64 heading West, probably I-70 straight through would be fastest, but would I-255/270 have less traffic at any given time on any given day of the week?
I really recommend the northern most "bypass." As noted, it is still busy, but imho not as "dangerous" as going through. Take 270 and then 370 West... It's not fun irrespective. I have almost always ended up coming to a stop at some point going through the middle.