The very fact that the GBA version was multiplayer-only, even when it was first released. For introverted players or people who just didn't have any friends with Game Boy Advances, playing the game was pretty much impossible. Even if you forked over enough money for three more GBAs and four wireless adapters, trying to play the same game on four controllers at once isn't exactly a manageable task. So if you don't happen to know anyone who can or wants to play the game with you, you're effectively locked out of the bonus content in the accompanying port of The Legend of Zelda: A Link to the Past without hacking. The fact that the Game Boy line's been discontinued for several years only adds to the problem nowadays.
For solo mode, switching. This wouldn't be a big deal, except for the fact that the shoulder buttons are notoriously weak on the DSi line, leading to many deaths when switching at critical points fails to work. It's better on the 3DS though.