Personally I'd do fine with lower federal taxes and less corruption in the federal government (two distinct yet correlated things). Keeping the federal government out of individual lifestyle choices is also rather high on my list.
As a corollary to that, a big issue personal to me is ending the war on marijuana/hemp. Not primarily because I think it's a harmless recreational substance when proper moderation is employed, but chiefly because it is one of the cheapest and easiest-to-grow sources known for industrial fiber and organic oil, and because there are sick people in pain and dying that could be helped by it but are instead being jailed. Its illegality was enacted based on racism (vs Mexicans/Blacks) and corporate lobbying, and the only real reasons it continues to be a Schedule I controlled substance is due to lobbying from tobacco and pharmaceutical companies, alongside reefer-madness style propaganda from right wing and law enforcement groups; polls indicate that the vast majority (80%+) of Americans support allowing medical use of marijuana. It bothers me that such a vocal minority is able to influence the federal government in such a large way, and this is why it is a hot button issue for me: Money shouldn't talk as loud as it currently does at the federal level, and the marijuana war is one of the most outstanding examples of what is wrong.
As it stands, we are excluding from general consideration one of the most all-around useful plants that exists on the planet, and the only current arguments for that exclusion besides lobbying and religious arguments is a shaky case that individuals are unable or unwilling to regulate their recreational use of the substance, that such individuals become a burden on society through crime and through welfare, and that it is the federal government's place to perform this regulation.
My opinion is that we should punish crimes regardless of who commits them or what they were on at the moment, that drug use is not an excuse for an insanity defense, and that felons convicted of violent crime should lose their right to imbibe since they have already proven themselves dangerous to others; I also think that in order to qualify for welfare, a prerequisite is that testing for recreational drugs should be performed, and welfare checks withheld in the case of a failure -- I don't particularly like the idea of subsidizing others' lack of motivation (which happens to be a principal side effect of the abuse of marijuana); I also don't think it is the federal government's place to set a default drug policy for the states - setting such a policy and enforcing it should be left to the states (and indeed, there is no constitutional support for federal government interference in this area besides the "general welfare" catch-all clause).
I support all-out legalization at the federal level (with appropriate taxation and regulation by the individual states), but I would settle for it being rescheduled to Schedule II. That way at least growing the plant would not be illegal, and patients could obtain their medicine through a doctor's prescription without federal interference. Other than that, I don't see a particularly compelling case to put nonviolent marijuana users/growers in federal prisons or to place them under various other deterrent penalties (such as loss of federal finanical aid for students).
The Libertarian party supports this issue in particular, and conflicts with other aspects of my political outlook in no noticeable way, so they will get my vote this fall. Hopefully other issues related to corporate lobbying and interest group influence will also be resolved through electing principled politicians who make a point of refusing any form of financial contribution.