I'm playing Baldur's Gate the first time (original not EE) and I reached the Marek and Lothander quest. I decided to respond "sure I'll help" as the safe route but hm... judging from what I read on the wiki if I rebuked him and did not keep any previous saves, then I'd totally screw up my game? Or if I only had a very old save, I'd have to waste time replaying a huge part of the game?

If so, that seems like awful design. Even more frustrating than that one npc insta-ending game by killing my main char during a dialogue regardless of the option I take, forcing several reloads.

I have played some Infinity Engine games before and I'm used to reloading every few minutes, but this is extreme.

I messed up my game too by killing Lothander the first time my party met him and had to go back to a save from long time ago.

It is a badly designed quest.

***** SPOILER *****

The bad design comes from two things, as I see it:
1. The 'antidote' is irrelevant... never used. Talking to Marek (after doing Lothander's quest) is what cures the party.
2. Marek is removed from the game until you've completed Lothander's quest, meaning you're in a no-win situation, *unless* you kill them both at your first meeting.

Very poor.

Oh, so if I replied something rude during the first encounter I would initiate a fight them, kill them and never receive this quest in the first place? Interesting.

Anyway, any other situations like that I should be aware of in advance?

It's too big of a game to be replaying huge swaths of it just because I saved a game after a dead end.

As far as I can remember, this is the only quest that can break the game.

Phew.

the fun bit kicks in if you play sod without finishing the quest because the timer is still counting

Do note that even if you mess up that quest, it's pretty easy to just edit your savegame via Shadowkeeper, so you don't have to actually go back to an old save. It's true that quest is just bad design though.

Yeah, but I don't like using third party resources... That's why I decided to skip on modding, the huge amount of options just gave me a headache. I would have probably dumped the game if the above happened to me (though maybe to return later, who knows...)

I never had problem with that quest. You just need to make sure that you don't kill Lothander and don't waste too much time after you meet him alone.