This is an interesting prompt because there's not a huge amount of established 'canon' dynamic to play with, which ends up being the whole point. You've got two incredibly earnest, heroic dudes with wildly different trajectories. Their brief interaction in the overhaul arc is devastating precisely because Mirio loses everything right after demonstrating the pinnacle of what Deku is striving toward.
So, the most resonant theme has to be Mentor/Protege, but pushed way past the standard framework. It's not just about teaching technique; it's about the terrifying weight of inheriting a legacy under the worst possible circumstances. A story where a quirkless Mirio, post-overhaul, has to guide Deku while wrestling with his own grief and absence from the field is brutal and fertile ground. The pairing dynamic becomes less about romance initially and more about this deep, traumatic bond forged in shared loss and a singular, crushing understanding of what 'being the symbol' actually costs. The emotional intimacy from that could naturally evolve into something more, but the core is that shared burden.
Alternatively, a 'Role Reversal' or 'Butterfly Effect' theme is super compelling. What if Mirio kept his quirk? Does Deku's path change with a truly unshakeable senpai constantly at his side? Or darker, what if Deku was the one who faced Overhaul first and lost One For All? Exploring a universe where their fates are swapped forces a deep examination of their characters stripped of their canonical power sets. The romance there would be a slow, painful build from mutual recognition of the other's shattered potential, a kind of 'we're both broken in ways only the other can see' vibe. It's less sunshine and rainbows, way more angsty and psychological, which for some writers is the whole draw.
There's also room for 'Fixing It' or 'Time Travel' themes, though they need a careful hand. A future Deku going back to prevent Mirio's loss is classic, but the real tension comes from whether changing that event creates a better world or inadvertently makes things worse. Does a saved Mirio alter the events leading to Shigaraki's rise? The relationship becomes a secret anchor point across time, a quiet promise that one person's suffering is worth undoing all of history for. That's some heavy, epic-scale romance right there. I'm less interested in high-school AUs for this pair; their heroism and the specific weights they carry are so integral to who they are that stripping that away feels like it loses the essence.