OP, I'm not sure what you mean by mainstream. Isn't mainstream what the Wii was? Casual gamers? You're probably referring to the popularity around big name titles like CoD, Mass Effect, Halo, etc. and their more realistic mature themes. Nintendo could do this, but that might not work as their user base probably doesn't want that and the user base that does probably doesn't want a Nintendo console regardless of a few new IPs, but I could be wrong and doing that might really help the Wii U look like an option.
The loss of third party support, which is what the Wii U is facing right now, is a mixture of lack of interest from the target market and Nintendo's choice of hardware. I think they made a poor choice in their architecture, design, and hardware capabilities. Wii's success rode on the wide adoption among casual gamers who have happily jump on the mobile bandwagon. Nintendo betting on their tablet controller was obviously the wrong move but they will still have many opportunities to change that over the years. Strong software support and updating functionality will determine the Wii U going forward, but as it looks right now Nintendo might have to go back to the drawing board in a few years time, no shorter than 3 years.
Even if Nintendo doesn't manage to attract gamers who would buy CoD everytime it comes out or similar titles, they really need to increase its install base so that those big titles and other more tailored ones from large publishers make it to the Wii U.