I made a Su4 a long time ago when I played RUN more frequently. RUN doesn't really take a ton of damage anyways, but the Regen ticks add up. I think I was able to get like +80~ tick Regen IV with Embolden. RUN can also wear some pretty good idle Regen+ gear, even to tank in (Futhark Coat +4, Turms+1 Hands/Feet, Null Masque), plus you get 3 from Auto Regen trait. This is the set I use for when I self-cast my own Regen, just downgraded Sword and Earring (and I haven't upgraded head/legs to +4 yet).
ItemSet 370264
The sword is also BIS for SIRD if you're swapping weapons anyways, has a chunk of HP so you don't dip too low in your pre-midcast sets, and is the BIS for Vivacious Pulse (a nice one-time heal when needed) otherwise. I never bothered to buy the HQ2 only because I rarely play RUN to begin with, but if you want to optimize, it for sure is better than nothing. Hard to quantify "large difference", but it helps keep you HP positive and requires less frequent healing. It's also handy for times when you pop Sforzo or any damage-immunity/heal moments (Shadow Ring, Turms Mittens/Empyrean proc) and can recover some health when things go left. Wouldn't personally say it's unbelievably worth a few extra Regen health ticks (reason I went Su4 instead), but certainly has a use case.
