One thing no one has brought up is nuclear fusion, not nuclear fission.
Some scientists at MIT came up with this idea: Use a vast number of huge toroial magnets, forming a cylindrical chamber, to contain the fusion reaction. Because you could adjust the strength of the magnets, you could spit the energy out the back, and because of the toroids you could slow down the output of plasma so as to avoid squishing. Of course, fusion is not that efficient, but if you just spit energy out the back you can actually get a reasonably effecient engine.
Then again, a generic-variety fusion reactor would allow us to reach anywhere, providing we can A. sustain fusion and B. get even a 1% more energy out of the reaction than we put in. A fusion reactor, although ridiculously dangerous, is hardly any worse than a missle welded to your ship (a.k.a space shuttle) and puts out very little radiation.
Of course, for the time being, an Ion drive with some VERY big solar panels is perhaps the best option for an interstellar spaceship. Although a large greenhouse (sustained by the solar panels) to supply oxygen and food would be needed, as well as a vast supply of expendable repair materials.
Also, there is the problem of high-speed interstellar particles, which can cause brain damage, amongst other things. In order to slow them down, you would need a lot of water. Perhaps you could make a giant water compartment encircling the living quarters, and fill it with algae to convert carbon dioxide to oxygen, with a reflective layer on both side to bounce back in light produced by LED's. Over this, you would most likely need an inch of lead and several feet of soft foam to protect against interstellar debris and radiation.
Just my two cents.