In the real world, people had all sorts of wacky ideas as to what would stop magic. The touch of cold iron, a line of salt, a horseshoe above the door, things like that. Probably a lot more in cultures other than Western European as well. Now, D&D and LU don't have those sorts of weaknesses as part of the rules, but it wouldn't be hard to homebrew them. The touch of cold iron on an illusion requires a concentration check or the illusion is dispelled, for instance (even if it's not a concentration spell). I wouldn't add such rules to an existing game unless the players were cool with it, but for a new game, sure.
Also in D&D and LU, well, since magic exists and actually follows rules, then at least some of those rules will be known, unless spellcasters really go out of their way to prevent the mysteries from being exposed.
Or optionally, people might be so paranoid about magic that anything out the ordinary could be seen as potentially dangerous. Communities could have contingency plans as to what to do should spellcasting be suspected. This could be bolstered by having natural things that reveal the presence of magic. In one of the Ravenloft Gazetteers (the one for Tepest, IIRC), there were mushrooms that slowly grew around the homes of spellcasters and people who had consorted with the fey. Something similar could very well exist in a more typical setting, which means that anyone whose home (or room at the tavern) has some of these mushrooms growing around it would be automatically suspected, which may give people an expertise die on certain saves against their spells.