Can only be done by a plugin which first removes the original relation, then adds the custom one. Or you could try to flag all relations as 'IsCustomRelation' (using the property IsCustomRelation) on the EntityRelation objects with a plugin, though I wouldn't advice it.
Our advice:
Use FKs when possible. Try to use a schema which is as perfect as possible, and use that for development. If in production FKs are missing, thats not important.