Superboy Prime is simply too powerful for Thanos. He's not only more powerful (moving planets like chess pieces, going toe to toe with friggin' Guardians, defeating Ion, defeating Monarch, destroying planets like a bowling ball knocks down pins)... he is also more durable (e.g., surviving a universal explosion and showing no signs of visible damage, flying right through Anti-Monitor's armor without disintegrating, saying that Black Adam's punches tickled, surviving a pile on of Earth's heroes while weakened with no sunlight....)
I know Thanos is powerful, but his high-end feats are because he always has some temporary power-up like an orb to help against Tyrant, the Guantlet against Earth's heroes, etc. Plus, he bled when going through a black hole, this would never happen to Prime. I also think Thanos' durability was because Death never allowed him to die, but as soon as she was willing, a top tier punched through his chest rather easily. Bottom line, if the Guardians, GL corp, Sinestro corp, JLA, and the rest of Earth's heroes did a pile on against Thanos, the Mad Titan would go down in a flash. Prime held his own and it took a Guardian's self-sacrifice to win via battle field removal.