I am a DO that's in NICU fellowship now, having only taken COMLEX. The only thing I can offer is my experience.
I barely passed COMLEX 1. There was a fire in the building during my test, and I refused to have 7 hours cancelled out and sit again. Being from PA, I also wanted to ensure I could secure Resolution 42 to practice in the 4 or so states that still require it. I basically called up 100 programs east of the Mississippi and asked if their previous DO residents had gotten Res 42. I ended up with 10 programs, 9 of which offered me interviews. I matched at my #4 - medium sized, Great Lakes region, not particularly well known, Level 3c NICU, no fellows to steal my procedures, but BAD boards pass rate and poor program management.
A lot of residency is what you put into it, who you can get as a mentor, what kind of letters they write. I worked hard, showed my interest in NICU, got a publishable research project. My COMLEX II & III scores went up 100 pts each. I passed my Peds boards without a problem.
I actually had to cancel fellowship interviews because I got so many offers. I ended up in a well known east coast program, my #2 fellowship choice. I have no doubt that it will allow me to work in whatever setting I choose, the biggest academic Level 4 or private Level 3.
So, for me, USMLE wasn't necessary. I put some heavy restrictions on myself for residency programs. I wasn't at a particularly good or well known program. But I made an impression and worked hard to get where I am.