A lot of the time, or at least in his most famous stories, Thanos has some kind of power-up item making him a lot stronger - Cosmic Cube, Infinity Gauntlet, Heart of the Universe (right?) . . . I don't know enough about the Penance Stare but if it's a magic/somewhat religious power then yeah, I'd say they'd probably work against Thanos. The way out of it, I think, for a writer who wants Thanos to remain pretty much unbeatable would be this: Thanos might not
feel any guilt at all for anything he's done. He's tried to change his ways before (though that's usually been retconned) so we know that he's
aware that he's done horrible things, but Thanos is supremely selfish and doesn't seem to view other people's lives as as valid/real as his own, and sometimes even views it as relieving people from their suffering (whether they believe it or not). It would be interesting if he did feel guilt because he seems to pride himself on his rationality and logic, being above the petty and senseless influence of emotion
(which he leaves to his brother - or at least should, since I think together they'd be more interesting than they are apart - I always talk about that potential though. Like, 5/6ths of what I post is about that, because there's just so much opportunity there - like, for instance, they're both actually motivated by the same thing: love).
But let's be real about Thanos for a second here, at least regarding his love of Lady Death. I don't see some kind of deepness to him here other than immature entitlement. Lady Death has made it
very clear that she doesn't like him! But he keeps trying to woo her, then gets angry when it doesn't work . . . He's acting like one of those annoying/creepy guys who doesn't understand that "I'm not interested" does not mean "convince me to like you." It's that whole hero trope of "achieve the goal, get the girl's love as the prize" thing that's in every movie. It doesn't work, Thanos! No means no. Leave her alone.
I haven't read Thanos Rising, though. I know that his backstory was changed, but his backstory/the explanation for his madness/the origin and nature of his relationship with death is changed all the time. It'll probably get changed again in the Thanos Annual that's coming out in a couple of weeks (!).