Thanos is so tied to the Infinity Stones that he made a new one: the Death Stone. Thanos has used the Infinity Stones to incredible effect, but he's also been defeated time and time again.

Mephisto has reality-mangling magic that makes him much more powerful as a being. Perhaps Thanos could have the physical edge, but he hardly has other powers without the Infinity Stones.

Just like in their fight without the Infinity Stones, Thanos will have to face his demons. However, the Reality Stone is a massive wild card, as it may shut everything down and allow the villain ...