Well, here's a thought...
When Generation One came out, the only option was a male trainer, i.e. Ash. They didn't introduce the concept of female trainers until Crystal in Gen Two, hence the creation of Misty for the anime.
Gen Two, as mentioned above, didn't have a female trainer until Crystal, and the anime was well into Johto at that point, so they kept Misty around, and the Crystal female trainer was in a couple Chronicle episodes.
Gen Three came around, introduced May as the female trainer and left Misty behind. May was around until Ash decided to go to Sinnoh.
Gen Four introduced Dawn for Sinnoh, and she'll likely be around until the end of the Sinnoh region, and perhaps a return to Johto (assuming they do one as they brought in Lyra/Kotone from the HGSS remake for a few episodes, which could do the trick if you don't count the Battle Frontier/Johto contest angle) but then will most likely be replaced by the female trainer in the fifth generation.
Personally I wouldn't mind Dawn staying around, but I wouldn't have minded May staying around either and she was replaced, so I see the same thing happening with Dawn, with a story arc in the new region to bring her back at least once. At best a new girl might be a dual trainer/contestant, but I suspect the contest angle is here to stay as long as the games use it, and I don't believe the games will stop using it.
Whether anyone likes it or not, Ash is the main character and he will be around until the end of this show. Case closed, end of story, move on.
As for Brock, could they replace him, perhaps. How successful it would be is another matter. They already tried it with Tracey and it was my understanding that it was not successful (I had no problem with it but I grew up watching Power Rangers, where the main characters got replaced basically every season after the third MMPR) and the odds of it being successful now is a million to one.
Especially in light of the threads you can find of Misty vs. May vs. Dawn vs...whoever else will come along in the future. And I imagine somewhere there are Brock vs. Tracey ones, do we really wanna add another person to that list?