Single-subject rules are adopted in many state, and they are neither complete solutions (viewing substantive subject-mixing as a problem), nor without their own potential problems. (And, anyway, to actually be mandatory, for Congress such a rule would have to be adopted through Constitutional amendment.)
Further, its quite arguable that substantive subject mixing is not a problem, poor representation is, and trying to limit substantive subject mixing just creates a new problem; where reps are effectively representing the interests of their district, why shouldn't they be able to effectively legislate based on considerations like:
1. X, considered alone, is better for those I represent, on balance, than not-X, and should be supported, and
2. Y, considered alone, is worse for those I represent, on balance, than not-Y, and should be opposed, but
3. X with Y, considered together, is better for those I represent than not-X with not-Y, thus, the combination of X and Y should be supported if X cannot be secured alone.
(While other representatives, with different constituents with different interests, see the same thing, but with X and Y reversed?)
If you could effectively prohibit subject mixing, that would prohibit compromises that are net gains for larger groups, even if smaller gains for the most-favored groups.
(Systems with parliamentary government with explicit coalition building essentially do massive subject mixing up-front in deciding the agenda of the coalition government when it is formed, and thus can avoid the need to do subject mixing when it comes to individual bills; the U.S. system works more on ad hoc coalition building, so the compromises are more on individual bills than anything analogous to the formation of a government in a parliamentary system.)