If mainstream means Tomb Raider, Grand Theft Auto or Modern Warfare-like sales, then hell no!
I don't see Metroid: Other M selling that well, and I see it being sidelined by much of the Metroid fanbase. If it is to sell well, it has to sell more to an audience that hasn't bought Metroid before than it loses in it's core fans. Which is possible, Metroid Prime is not that big and it's in decline, but I don't see it selling as high as the first Metroid Prime.
A game I'm developing with some friends:
www.xnagg.com/zombieasteroids/publish.htm
It is largely a technical exercise but feedback is appreciated.