Well, most often used professional way - is to make default content a mod too. That is fully handled by an engine as a mod, not separately from other mods that could players do. That's the way of games with most powerful modding capabilities like TES 3,4, Fallout 3, OFP, Armed Assault 1,2, Cortex Command, and others. So all challenges, weapons, monsters and other stuff should be placed in a separate mod file. Game should be possible to run without anything from it's original content.
Now about highscores and stats. I think that each mod should have it's own pair of highscores file and player info file. And that file should only be loaded if that mod is loaded. That file should contain all the things that are related to that mod - monsters, weapons, uniques, player ranks, achievements, and, practically saying, everything. Because ranks, achievements and stuff should be possible to change from mod to mod, and it would be a pain in the ass to check incompatibilities. What is without doubts - weapons/monsters should be output when viewing stats only from the mods that are currently loaded.
So, what we get in the end - pair of files for each mod. Now, the main thing: if you are running one mod, all the achievements, kills and stuff would be recorded to the according files. BUT if you would run 2 mods at a time, nothing would be recorded anywhere.
Pros: No cheating. Stats are recorded only if you are playing clean game, in the way that was supposed by it's author.
No restrictions in activating many mods. If you want - you can activate as much mods as you want and they won't ruin your stats, or anything, even in chaotic configurations.
Mods with just new monsters and items won't get any issues because they don't need special achievements anyway.
Cons: That would be harder to make mod that is just an expanding to some basic mod. Like mod that add several more high-level player ranks, or achievements. It would need to copy all the content of original mod (which wouldn't be hard), and it would still need to make some kind of converter of player stats from default mod to his one. Because otherwise it would require to start everything from the zero in that new mod.
So, if someone is making something big and want to use there his own achievements and ranks - he just copies required content from original mod file, and everything else makes by himself. And if someone wants to make just mod to play old DooMRL challenges with some new weapons, maps and features - he won't need achievements and ranks for that anyway.
So or make TC with everything included, or make small mods that won't be a pain to make/manage/add to the game.
What do you think?