Most printer kits come with a default configuration nowadays so you should be able to start printing with those settings immediately, but there are a huge number of adjustments that can be made if you want to. If you build your own printer from scratch, you'll build your own config as well, but you can still start with a generic premade Reprap config and adjust it to your specific machine.
Here's a few of the big settings:
BED LEVELING
A level print bed is *critical* to a well sorted printer. A slightly off-level print surface will make an otherwise perfect printer look completely awful. This is the #1 thing you should pay attention to, especially on a new printer. A perfectly level print bed solves many problems. There are some in-software solutions for this in the pipeline, but for the moment it's been a manual check-and-adjust process. It isn't difficult (typically just a turn of a screw here or there) but is overlooked by a lot of new operators. Remember, your whole print will fail if your first layer doesn't have a good base to stand on.
TEMP
Temperature settings are always being tweaked, as the ambient temperature of the room you are printing in changes so should your print temp - you want the filament to flow smoothly out of the extruder and then solidify as soon as possible after it has been applied. Too cold and your layers don't stick and the job fails; too hot any you get droopy melty ugly prints. A number of printers are using fans to blow directly on the print, to help the plastic cool down immediately without droop - this is nice as it allows you to print hotter than you would be able to without the fan, which makes it easier to print gorgeous super high resolution models.
SPEED
The feed rate of your filament determines the speed of your print. Faster is nicer, but you will likely find that higher resolutions and faster speeds are tough to get at the same time. Newer firmwares with acceleration features are making faster print speeds a default function, but more speed is always attainable if you put the work into tweaking it just right.
LAYER HEIGHT
Default layer heights are getting thinner, and this is what determines your resolution. The M2 default layer height is pictured in the post above, with 0.2mm layers.
With some time and tweaking (and a bit copying the settings from others that have already improved their resolution) you can get 10 times that resolution, or more. Here's what people were getting out of the Ultimaker a year ago:
http://davedurant.wordpress.com/2011/10/12/ultimaker-faq-but -what-about-the-quality-of-prints/
I particularly like the close-up comparing the print to his finger.... you can see how many layers per fingerprint groove there are, which really shows how smooth 0.02mm layers are. This was cutting-edge a year ago, and already it is attainable by pretty much anyone - if you're willing to invest the time to make it work. 20 micron layers aren't going to print fast, you'll be waiting for these to print for quite a while.
As I stated above, "1 micron" prints have been claimed recently... and even if they meant "10 micron" that's still twice the resolution of the print example above and 20 times the resolution of the example I posted a few days ago. See:
http://www.twitch.tv/woofpickle/b/331418167
That's a Makergear M2, and the resolution - whether really 1 micron or 10 - is amazing, and more amazing is his feedrate isn't too slow despite the resolution. I'm eagerly waiting to see some finished prints with those settings up close.
In general, extremely high resolution prints require more than just a tweak to the layer setting... everything else gets more important when you're working with layers this tiny, and bed leveling is hundreds of times more vital.
I recommend you research everything thoroughly, as there's a lot to learn. Check out the Google Groups for RepRap, Makerbot, Ultimaker, Makergear, and any other printer you may be interested in. The devices are all very similar, and the people are all generally very helpful.
As for design limitations... I guess I don't know what you're asking for specifically. I'd like multi-extruder print heads to really take off so support material removal becomes as simple as "toss in bucket of water." Much faster print speeds would always be nice, and bigger print surfaces are always welcome.
Alternate designs for home printing are popping up out there as well. DLP printers are extraordinarily high resolution, but also expensive and very small in print area at the moment. Powder printers may take off soon, as they don't require support so overhang and support removal issues are removed completely.
I think the biggest problem with any printer at the moment is they still can't make me "Tea, Earl Grey, Hot".... Yet.