I'll throw my results in because I hate when there's no resolution on these kinds of threads. L6 basically said that the noise was normal with my Helix LT. I ended up buying an EbTech hum eliminator and that removed my ground loop issues with the effects loop and send return. I still get some RF interference that's amplified on the higher gain settings of my Mesa Mark V but 4CM now works. On those high gain patches, I use a hard gate to kill any additional buzz and that's been quite enjoyable.
This ends up being a lot of cables for what was supposed to be a simpler set up (I've got short patch cables between the LT and the EbTech, longer cables to the amp and EbTech, but throw in that I am also using a voodoo lab control switcher to midi control my Mesa Mark V, with midi cable and 4 1/4" into the switches on the back, there's a lot going on) but since I don't play out so much, it's not so bad and it does sound really good.
I split my playing time between going through the Mark V and going direct through some Yamaha studio monitors. It's totally dependent on my mood of the day and what I feel like playing, even if I think the amp is still 5% better than the models in the LT. Unless I'm doing rapid fire AB tests, which aren't totally fair to the LT, it more than produces excellent tones that are inspiring to play. The Helix has completely replaced my pedalboard and the footswitch for my Mark V with the exception of a digitech whammy (the pitchshift is just not as good/clean/clear). I still have GAS for a Friedman Dirty Shirley to compliment my Mark V, but I'm also thinking about getting an FRFR solution like a DXR10/12 or Powercab for the helix because it's very good at the pallet of tones that the Mark V doesn't do so well (mid-gain, vintage voicing, M style types of things and some of the different cab types).