Highly unlikely this would happen. Malakian isn't the kind of style that MegaDave would hire for lead guitar duties. Still, I'll play along:
Megadeth's 1999 Risk album which was very "alternative" sounding compared to their normal stuff has greater success prompting Dave Mustaine to continue in that direction. Marty Friedman leaves the same year to pursue his Japanese Pop music dream like OTL. Meanwhile, System of a Down is less successful for whatever reason and Malakian, hearing about the Megadeth vacancy, decides to try out for shits and grins. Surprisingly, Dave hires him and Megadeth becomes much more experimental musically leading to old-school Megadeth fans comparing them to Metallica as to being sellouts while attracting other fans in nu-metal...
I don't know, I have a hard time seeing this happening.