The Silly 17th Amendment
If the federal government is a federal government in the strict sense of a league of sovereign smaller governments -- like the UN or NATO -- then it makes sense for the sub-governments to pick their representatives, and for them sub-governments to be represented equally. After all, we didn't hold a national election for a UN Ambassador to represent the people of the US. Instead, the Obama administration picked Susan Rice to represent the US government.
On the other hand, if the federal government is purely a central government of which states are administrative subdivisions, then Senators ought to be selected by, and represent, the people of the US equally. This is basically how the House of Representatives does it, and most states have their own legislatures composed of two houses that are both elected from equal-population districts. The Senate could still be more prestigious and smaller and have longer terms, but if the individual voters are going to select Senators to represent them, then everyone's vote should have equal power.
So we can represent the state governments equally, or represent the individual voters equally. In neither case do I see a rationale for why the people of California as an aggregate ought to have representation equal to the people of Rhode Island as an aggregate. Any attempt to point out the differing interests of people in different states would run up against the question: why not represent other interest group divisions, many of which are more significant than state differences, equally? We could make the Senate have equal numbers of Senators for men and from women, for workers and owners, or for Asians and Latinos.
My own preference would be to scrap the idea of tying Senators to states and make the Senate elected on a national proportional representation basis. But if Senators are going to represent states, it seems sensible that they represent the governments of the states, and thus be selected by them.