Probably too hard to alter the machinery of government provisions and about right to protect human rights protections.
I absolutely agree with the new guy here. I'm extremely wary about anything that could tamper with the Bill of Rights (and most other rights for that matter, of course). However, I do think the overall structure of the federal government is in massive need of reform and updating. The only significant constitutional changes that have been made on that front since the founding are the 12th and 17th Amendments, the latter obviously being of much greater significance.
Not to disagree with your overall post, but I'd argue the effects of the 12th Amendment were still pretty damn significant in & of themselves, given that who knows what kind of crazy-ass mishaps would've resulted had the original Electoral College formula's defect (that if each elector followed party tickets, there'd be a tie between the 2 candidates from the most popular ticket) not been corrected.