There are lots of detailing issues that blend together to form a realistic scene, but I think there are a few overidding principals that have a lot of impact and should be kept in mind.
One of these, and it has been mentioned, is overall blending of the elements. This really helps make a collection of individual models become one scene - pay attention to the colors used to paint everything, including the trains. Colors can all be slightly faded and grayed for 'scale perspective' and to suggest the effects of sun, as well as to help compensate for lighting at a significantly lower level than that provided by the sun.
Also, especially with scenery (and to a lesser extent, structures), the color palette should not be too disparate - this blending will tie everything together. Even lightly overspraying everything with a light dust color ties it together. Dave Barrow wrote in an article in Model Railroader that he mixes the same blue paint used in his backdrops into the tan paint he uses to adhere his sand, to help simulate the color temperature of sunlight and blend the foreground and background elements.
Within this overall blending, there should still be things that stand out on closer inspection. Look at a typical model RR tree or weed patch, they're usually one color of foilage, or at best, an even blend. Now look at real trees or weed patches - not only is there blended color variety, but there is strategic variation telling the story of what the plant material is doing. The new growth on the tips of tree branches is usually much brighter than the established foilage, and this often lasts long into the summer. Green strips of weeds in an otherwise dead field indicate the presence of water, or a low spot that retains just a little more moisture than the surroundings. Both of these effects can be achieved with simple drybrushing after the scenery is in place.
nkp174 mentioned that it's important no gloss paint is visible, but I would debate this point. It's true that nothing should look like glossy plastic, and that gloss scales down, so HO scale cars don't look right with a 1:1 Ferrari-quality paint finish, but I think that texture and gloss variation are important. Just look around on a bright day at how many things have a reflective surface - lots of new building materials (metal ductwork, painted metal roofs, glazed tile, windows, painted metalwork...), autos, new freight rolling stock (which have a shine very different from new plastic models), Bot's dots, signs (new acrylic store signs, as well as Scotchlite street signs (again, a very different reflectivity than shiny plastic)), reflectors on trains, broken glass. The latter is all over in the sand at the sides of many roads, and easy to model; moisten the area with dilute matte medium or white glue, and sprinkle on some fine clear iridescent glitter, then vacuum the excess when the glue's dry.
The next thing I think contributes to overall realism is lightness of materials, and by this I mean the importance of scale thickness. Fine, delicate details go a long way, and the play of shadow and light is very important. Wherever possible, details like etched gratings and walkways, where appropriate) go a long way. Being able to see through things makes a big impression - on of the really nice things about Central Valley tie strips is the way the web is molded, so you can ballast track to a level below the tops of the ties, and see under the rail. Also, and this has been mentioned, stringing powerlines across all those empty poles goes along way. Especially if you use multiple line thicnkess and replicate phone lines, cable lines, junctions, catenary for long spans, etc.
The final area I point out for now is that too much compression, and cramming too much track and trains in to a given space, spoil the realism very quickly. For some, the additional switching and spotting is more important than realism, and that's fine. But the most realistic layouts generally seem to minimize the trackwork and have lots of open space. Take a look at how realistic Gregg Fuhriman's Glen Frazer Freemo module is, with its looong, smooth, sweeping trackwork and landscape, here:
NorCalF Module Information
Large buildings and roads add to realism, too - think about how wide a typical city or suburban street with parking on both sides and a turn lane actually is, and also how long elements are; one of the most unrealistic things I often see on model RR intersections are very short approaches for turn lanes - the curve in the double lines should flow, just like smooth trackwork.
Well, that's my rant for now - I hope there's some useful info there.
Chris