Treat it as if you were making a Super Reflexes character... you just do it in fewer powers. Here's a comparison from another thread that applies for both Night Widows and Fortunatas:
It's fairly easy to softcap with perma-Mind Link (with it active you get more defense than SR) but with controls you don't need to.
Many builds you'll find use Aid Self; you have the defense to use it fairly regularly but I've found that with the build I have I didn't need it, and often even skip using green inspirations just because the incoming damage was low enough that my regen (and Panacea proc) was keeping up with it once the scaling resistance kicked in. You can help the scaling resistance out with oranges, too, they usually affect my hp bar more than popping the same size green, it just takes a bit longer to get there.
What does kill you is bad RNG timing where multiple hard hits get through before the resistance kicks in but that's true for SR also.