Regardless of how senators are picked, it's deeply problematic if representation is so divorced from population size. Alternatively, if we insist on retaining a fixed number of senators per state we could strip the senate of essentially all of its powers (perhaps becoming more advisory in role, with only the capability to temporarily filibuster house legislation); but that strikes me as being even more unachievable.
But personally, I don't think appointed senators would practically help much.
The point of federalism isn't to achieve some ivory tower ideal of centuries past, but to have real value today. Some of the value we can still retain is flexibility: essentially letting states go their own way for many laws and regulations. That benefit of federalism is quite real, and imposes no requirements that the senate needs to have appointed senators vs. elected, nor that the number of senators be fixed (vs. scale with population size). I'm pretty sure we can mitigate the deadlock, lack of accountability, and undemocratic representation issues with today's congress+executive while also eating our federalist cake.
To be clear: I don't think of this is worth pursuing as political reform; it's entirely unachievable due to the US's virtually unamendable constitution (basically only populist amendments are ever achievable, never this stuff; states need to large agree, after all - and pure political power play makes that utterly impossible).