With What If...? teasing Ego and Thanos on opposing sides, the question of which omnicidal force of nature would prevail narrowly favors Thanos.
Episode 2 of Marvel's What If...? featured a mostly reformed Thanos, and a cameo of the villainous Ego — but if these two MCU villains were to fight, whose power would be stronger, and who would win? Leaving aside Stan Lee's oft-repeated wisdom that the answer lies with whatever character the writer wants to win, examining the characters from their MCU incarnations allows for some comparison — and the possibility of a match-up. Since both characters have high and low points in their story arcs, it is fairest to compare them before their schemes hit their peak: before the events of Avengers: Infinity War and Guardians of the Galaxy Vol. 2 respectively.
Ego is capable of rearranging the matter that composes his being, has a galaxy-spanning intellect and an entire planet for a body, has an obvious advantage over Thanos. With the brief exception of Peter Quill, however, Ego has no collaborators or competitors for his power; Mantis is Ego's only living companion in Guardians Vol. 2. Thanos in contrast leads an army: in addition to Nebula, Gamora, and the Black Order, he has a fleet of ships and a massive fighting force of Outriders. Personally, Thanos is physically and mentally superhuman, capable of overpowering the Hulk and the Asgardians that he casually wipes out. Taken as individuals, Thanos is easily overpowered, but with all massed resources on both sides, he is marginally capable of overcoming Ego.
The trick to Ego's initial advantage rests in his ability to conjure forth matter and exert absolute control of it across his form. In order to do any lasting injury to Ego, Thanos would have to injure the brain of a living planet, which would require him to first discover where it was, and then fight his way through millions of tons of earth and stone to reach it. Without the Infinity Stones, Thanos' superpowers are no match for Ego, doubly so if he does not have support distracting Ego, as the Guardians of the Galaxy did. What circumstances might conspire to have Thanos in such a position to begin with is another question, but it is fair to say that as ruthless and experienced as Thanos may be, Ego has several more millions of years of life experience.
Ego's strength — his solitary nature and absolute control over the environment within his sphere of influence — is also a weakness when facing off against a properly prepared foe. For all of his antisocial ideas about population control, Thanos nevertheless has a great many followers and proper military force to bring to bear. Unafraid to risk casualties even among his own forces, it seems likely that Thanos would take a page from the book of Ronan the Accuser and lead with orbital bombardment. Thanos' flagship in Infinity War, the Sanctuary II, serves both as a carrier for smaller craft — which could help to intercept any countermeasures Ego might launch — and as a bombing platform to open up Ego's crust enough that Thanos could then reach his brain.
Even without the infinity stones, Thanos was a force to be reckoned with; although personally powerful, a great deal of that strength stemmed from his position of leadership within a force feared through the galaxy. Ego's nature — and his ultimate scheme — both keyed around the fact that he acted alone. As potent as Ego's Celestial powers may be, Thanos' power is both internal and external, and leading the charge against Ego might not require him to be in a position where Ego could bring his abilities to bear; something a future What If...? might do well to consider.
