I'll try to keep it short and sweet to avoid getting off topic (remember, this is about Serena), but 1. Even for a newbie, it should have been fairly obvious what would happen with birds and bugs if they got together. And yes, she definitely was in the right for telling him off that instance. If she sang praises for him and his frankly stupid action with Caterpie (not just ignorant, but genuinely stupid. Honestly, even if I were a rookie, it would be common sense to not use a Caterpie against something that would most likely eat it for breakfast and thus I would know full well not to use it, and instead choose Pikachu for the battle.), that would be even worse.
And besides, having them constantly singing praises for Ash would in fact be worse. Don't forget, the main villain Gaston from Beauty and the Beast had everyone singing praises for him, them never saying no to him or talking him down or anything like that. The only one who did actually do any of that was Belle (and that reminds me, what she did to him, jerk or not, was actually worse than what Misty did, as she never said no to him before throwing Gaston into the mud pond, and actually took amusement in his falling into mud), is ultimately what resulted in him becoming a huge jerk and later the main villain. Do you really think that's a good idea at all, especially when that's exactly what would turn out as a result? Besides, there were plenty of times Misty and Brock actually supported Ash (like Cinnabar Gym, and heck, Pewter Gym where Misty actually offered to help him out), why do you constantly ignore those anyways. Oh, and BTW, Misty definitely doesn't abuse Ash much anymore, and honestly, her temper was actually arctic compared to Naru Narusegawa, for example or Jessie even. Even if she doesn't return to the series, she really should at least actually be allowed to pursue her dreams rather than be cooped up in a Gym. Not to mention Misty and Brock were caring trainers at heart as well (or have you not been paying attention to their good-hearted actions in several episodes).
2. Playing that kind of prank was actually extremely mean-spirited especially considering what they were about to do and what had just happened earlier, it doesn't matter his reasons (and BTW, had Misty or Brock done what Ash did that time, guess what, I wouldn't have any sympathy for any of them either).
One last thing, technically, he isn't the main character of the games (First Gen and possibly FireRed/LeafGreen? Possibly, but definitely not Generations 2, most of 3, 4, 5, or 6), and in fact you can do the Pokémon journey yourself. Just take out a Gameboy/Gameboy Color/GBA/DS/3DS, start playing a Pokémon game of the Core regions, and you're all set to go on a Pokémon journey yourself, or at least the closest to doing so in real life.
As far as the topic, the only things left is making sure Serena has actual development (not to mention actually given something that proves she isn't a Hina), that she actually gets a goal, and that she at the very least trains the Pokémon she has.