As much as I love Thanos he wouldn't stand much of a chance. Maybe one on one it would be different. Moondragon and Gamora could probably do it with just the two of them working together. Just use the mind gem to distract him while Gamora kills him with the Godslayer. If you wanna make it interesting since Moondragon gets to keep the mind gem let Thanos keep the Reality gem.
If I recall that thing did jackshit to his skin in Thanos Imperativ.
__________________
I am in your algorithm learning all your mannerisms
I'm already level with God
A million words a second and I know your imperfections, baby
I'm the only future you've got
Speak in diatonics, motivation diabolic
I'm like a religion, better locked in a box
Picture perfect image, more powerful every minute, baby
I am everything that you're not
He doesn't,and it broke on his skin when she tried to kill him with it during Thanos Imperative. And he also killed Gamora before when she tried to kill him with it years ago in a Marvel 2in1#2