Term limits for members of Congress. Nothing too short, nothing too long. I'd say three six-year terms for Senators and nine two-year terms for Representatives.
Federal judges can serve no more than 15 years in any appointed position.
Abolition of the Electoral College. From then on the President and Vice President will be directly elected by popular vote.
Replacement of first-past-the-post voting with either Instant-Runoff Voting or Approval Voting (both have their advantages and disadvantages).
Redrawing of congressional districts should be carried out by nonpartisan commissions using a neutral mathematical algorithm (such as the Shortest Splitline Algorithm).
Elimination of corporate "personhood." The rights and privileges guaranteed by the Constitution should apply to natural persons only.
Actual campaign finance reform. Only natural persons who are legally eligible to vote may donate to political campaigns. There should be reasonable limitations on how much people can donate. Increased public funding for political campaigns. Each candidate should be guaranteed equal airtime.
A balanced budget amendment to the Constitution. The federal government's budget should be balanced at the end of each fiscal year. Deficit spending will be allowed in the event of recession, national emergency, or war (only if formally declared by Congress; police actions and vague "Authorization for Use of Military Force" acts like what got us into Iraq and Afghanistan won't count).
If Congress fails to pass a budget on time, then they will lose all of their benefits (salaries, healthcare, etc.) until a budget is passed.
The end of the two-party system, which would be enabled by removing the electoral college, replacing FPTP voting with IRV or AV, and increasing public funding for campaigns and ensuring equal airtime. Third parties would have a realistic chance of winning elections. We would have a center-right conservative party (the Republicans), a center-left liberal party (the Democrats), the Tea Party (split from the GOP), a social democratic party (formed by progressive Dems), the Libertarian Party, the Green Party, the Constitution Party, and who knows how many other parties.
An actual universal healthcare system. Something that's a fair compromise between single-payer and a market-based system. Right now I'm partial to Germany's multi-payer system.
Ending the War on Drugs. Legalization of marijuana, LSD, psilocybin mushrooms, and other soft drugs nationwide. Hard drugs should be decriminalized, and their use/abuse should be treated as a health issue instead of a criminal one.
Implement a Negative Income Tax, which combines elements of a progressive tax, a flat tax, and a basic income. It would allow us to eliminate welfare programs (minus entitlements), thus saving the government and taxpayers money.
Eventually implement a Universal Basic Income for all Americans (or at least all legally eligible adults). This will become necessary as automation eliminates many jobs in the coming future. The aforementioned NIT could serve as a stepping stone toward UBI.