Okay, so Hero Factory won't return as is - what if it got a 'successor theme'? We've seen this with Power Miners and Rock Raiders, or how we've cycled through various Castle and Racers themes throughout the years. Remixing older themes into newer styles is historically something we've seen a lot of. Bringing it back as constraction is likely out of the question - Lego has shown they don't have much interest in maintaining the style in any sort of mainstream way. This wouldn't be a straight reboot, either; the above examples shared concepts, not characters.
Honestly I could see Hero Factory meshing well with Space Police, or perhaps even things similar to Metru Nui from Bionicle. It could be a group of intergalactic crime-stoppers, but with more individuality than we got from the heroes of Space Police. Or maybe it would amplify Metru Nui's dystopian vibes, with the robots being an elite squad that enforces the government's rule in a sort of cyberpunk world. And those are just two ideas off the top of my head; there are all sorts of ways Lego could remix and mash up Hero Factory to make it new and exciting again.
There is, however, one problem that I could see with this concept: the character design. Hero Factory introduced CCBS, the Character and Creature Building System. Part of the allure of Hero Factory, and constraction in general, is the freedom you can have with how the characters themselves are put together. You can have Bionicle classics like Brutaka and Toa Mata Nui, or break from normal builds with things like Keetongu or Gadunka. What does system have? Minifigures. Don't get me wrong, I love minifigures. Their simplicity is one of their biggest strengths, in my opinion, but in this case it's a huge problem. The options for customization and uniqueness in character design become minimized, relying solely on custom prints and hairpieces. It's very limiting for an idea that's used to having a lot more freedom.
Would it kill the line? Probably no more than Lego's seeming unwillingness to advertise any original IPs outside Ninjago. But it does make me a bit sad that constraction's brand of unique character designs is starting to become a thing of the past.
So could Hero Factory come back? Definitely. Would it look the same? Probably not.