I fly for a charter/fractional operator and thus have a lot of legs that are from/to unusual city pairs.
TL;DR: Preferred Routes if they exist, Previously Cleared if they exist, and then building my own route from the ends toward the middle using things previously cleared in/out of nearby airports plus choosing my own enroute fixes.
If it's in bigger metro areas, I'll check preferred routes (from the A/FD aka Chart Supplement) first. Those are what you're going to get anyway, so you might as well file them. At that point, that's the end of the process, you're getting that route, period, end of story, like it or not. Maybe a nice controller will give you direct farther down the line, or give you a better arrival route once you're in the same ARTCC as your destination, but you'll be flying it mostly as-is.
Otherwise, next I'll look at ForeFlight to see if anyone has flown between those airports, and what route and altitude they were cleared at, as well as the number of times that routing was issued - Often there are weird one-off routes that someone filed for weather, and I don't want those unless I'm the guy dealing with the weather. These routes will also often show some commonality; for example when I was planning one of today's flights I saw that there were 11 routes; two started with REVSS CTR HNK (cleared 6x total) and the other nine were all some variation on HYLND MANCH CAM or HYLND MANCH SYR (cleared 139x total). So, I have a good idea that I've gotta start with HYLND MANCH or they're just gonna give it to me anyway.
Often, if I'm not getting any previously cleared routes, I can look for busier airports nearby either the origin or the destination and figure out what the departure and arrival fixes are for a particular TRACON (if I'm landing inside a TRACON's airspace), then I can use those fixes. They exist everywhere but don't seem to be published anywhere. For example, going out of my base of KMKE, southbound I can use the UECKR6 or ACCRA5 SIDs, but eastbound I'm going to get SQUIB, northwest I'm going to get HAWKN, west will be GREAS JAYEX, etc no matter where I'm going. Likewise, on arrival I can either use the GOPAC2 STAR from the south or west, BRAVE EXARR from the southeast (usually preceded by VINNE), GETCH LYSTR SUDDS from the east, and so on. Obviously the SIDs and STARs are published, but those other routes are not and really won't show up anywhere except previously cleared routes.
Enroute, if you're not flying within a couple hundred miles of a busy Bravo or on the east coast, you'll usually get as filed... So, I'll look for either SIDs or STARS if they exist, or the above commonly used fixes (usually 2-3 fixes at each end), and then file one convenient high-altitude fix per ARTCC in accordance with the AIM. Generally there's something within a couple miles of my route, but sometimes I'll move the route line over a little more to avoid going through the corner of ARTCC airspace to make ATC's life easy. For example, I've used GORDO to get handed straight from ZAU to ZKC without having to go through ZID.
And, yeah, I've filed some fixes just because they're funny. Getting cleared "Direct Crazy Woman" or hearing "Report the Flippin' VOR" is always fun.
(Sadly, FLP VOR does not exist any more.)
And after all of that... Sometimes it'll still get changed, because the FAA likes to act like the Wizard of Oz and keep all of their stuff behind the curtain.
