Heh. I have to weigh in on this question, just because it's what I'm (sort of) working on.
I suggest that we'll eventually make it to Pluto and beyond, but we'll likely end up doing it in "generation" ships. I can't remember who came up with the idea, but it would essentially have to be built in space piece-meal, be provided with a nuclear reactor of some sort (more on that later), be provided with some sort of self-sufficient oxygen creation system (I recall a mention of greenhouses elsewhere - that's not too shabby an idea), strict population control measures, food (there's the greenhouses again...) etc. etc. etc.
Nuclear power is a dirty word in some books, but as far as I know, it's hands down the most efficient mass->energy conversion system we've got available to us right now. You can haul a relatively large amount of fuel for a much lower cost than say, LOX/LH. Assuming that future technology can miniaturize nuclear reactors, even scaling down to a tenth of the size for the same power, it can be made useful for an application like this. If the process can release more energy per unit of mass safely, it will be made even more useful. Keep in mind, the actual numbers are for engineers - I'm just a visionary here.
Propulsion can be handled in a couple of different ways. Ion engines would be a natural for something with a nuclear power plant, I'd imagine. Low delta-v of course, but you've got a crapload of ISP to work with. Another suggestion that I've been working with myself is picking up solid water in Saturn's rings. I've been toying with the idea since snwcrsh reminded me (indirectly) of Asimov's story, "The Martian Way". Of course, it'd take an absolute crapload of water to get out of the orbit, but the chunks are probably fairly sized in the first place.
Assuming a fixed amount of thrust for a water/steam/whatever rocket (which I have no clue what it'd be...), even with a craptastical ISP, you've got a massive amount of fuel to work with. It'd take a while to get going, but once it's there, wooooo. You're moving, and you're not stopping for anything. :lol:
You're a brand new comet in the sky.
Added bonuses for this is that you've got all the water for crew/colonist/engine/nuclear coolant/whatever use that you could ever need at that point, and it's one of the biggest worries on a long journey like that. Add in recycling measures, and you'll "never" run out.
The greenhouses would of course have to run on fake UV and whatever else plants beg for. I'm not sure how big it would have to be, and if there would be any other measures taken. One thing is for sure, everyone would be a vegetarian, and would have to like soybeans. The only meat on that ship would be Soylent Green.

Another necessity would be rotation of crops.
I'm not entirely sure how protection from impacts, radiation, and whatever else the universe can throw at us would be handled. That's being covered in another thread IIRC, so hopefully the brain trust over there will come up with something useful to the issue.
A final thing to consider is the end of the journey. This thing would be absolutely freaking -massive-. You would either:
A: have to build it so it could be split into pieces at the end, and re-enter seperately, presumably with a drag chute of some kind. This would be a Bad Idea from a structural integrity standpoint most likely, but it'd be the most likely way that something would make it from orbit to the surface.
B: Provide some sort of cargo carrier so that bits and pieces can be taken down. This would be a crapload of round trips, not to mention the engineering problems that come about from stresses on the poor little cargo ships. I'm not even going to go into dealing with the landing area.
Another issue with 'endgame' would be that you'd have to basically start over. You'd have the knowledge, but you'd be lacking in the raw materials to start even a small village. Construction equipment (even if we're talking hammers and nails), more food supplies, etc. Personal experience tells me that building a base for 500 people (that's roughly what we had in Jalibah back when I was in Iraq) takes an absurd amount of logistical support. I don't honestly know exactly how much it was, but we had orders of magnitude more pieces of construction gear than we had communications gear (which is what I dealt with). Carrying this much materiel across the Atlantic was a fuss. Carrying it multiple light years would be a

horror story.
On the more theoretical side of things, players of Sid Meier's Alpha Centauri would have a feel for the problems of starting on a new planet from scratch if they read the tech descriptions - ol' Sid and his team had a pretty good handle on the problems, although he had a much bigger ship to work with.
... holy crap, I rambled. Posting now, 'kthx.