Purely discussing game divisions...Nintendo has and always will be the most profitable for one major reason. It is primarely all they have. Unlike Sony and MS who can leverage their other multi-million dollar profit divisions, Nintendo only has games. That is why they make the best 1st party games, if they don't they will not succeed as a company. All of Nintendo's consoles have been nicely profitable. Now, not only is their portable divisions pumping out the cash, but so is the console division. The next few years will show a hefty increase year after year for Nintendo's annual margins.
Sony and MS could not be profitable as underdogs. The 360 is by far a better bet on overall profitablity after R&D than the xbox but it will need to sell 20m to do this. The PS3 will need to sell 40m at least to recoup, however, they don't really need the PS3 to sell as much. Bluray will bank off of the PS3, even if it does not 'win' this generation. Even if they only sell 25m PS3's, that's 25m Bluray owners buying movies and downloadable content from PSN.
So to answer the question, maybe. If you are Nintendo yes. If you are following the business model of MS or Sony who don't have the total 1st party lineup of Nintendo (I don't mean 1 or 2 great sellers, but 10) then no you must be 1st or a close second.
