In theory they could do anything with the help of animation. It could even be set pre-Nemesis and actually incorporate Data in the cast too, because Spiner's concerns about being 'too old' to play an ageless android would be very easy to fix in animation. He would just have to sound young.
And they could modify the voices easily enough, so that's really not a big deal either. I think an animated series would do well. As long as the plots were serious enough, adult fans would watch it, and younger fans who've seen the Abrams films might buy in, too. Because it would theoretically involve only prime universe characters, some sort of explanation would have to be offered to fans who may be confused by seeing much older versions of the TOS characters (if any of them were to appear).
Having a huge crossover event would be much easier via the animated route. If the movie/TV pilot did well, it could easily lay the groundwork for another series down the line. Otherwise, the only way I could see a new TV series getting off the ground would be to feature an entirely new cast and group of characters. I don't know how well such a series would do outside of hardcore fans, however.
I think these are good points. to follow up, these days animation that skews older is still a niche market, but one important difference from the 70s, when ST: TAS was around, is that it's a much more profitable niche market than it was 40 years ago. Can it appeal to non-hardcore fans? Maybe, if the powers that be play their cards right, but the overall nerd culture (Trek and otherwise) has a lot more disposable income now than ever before.