I play to maximize score, and since character background, rise to power, and traits do not affect the difficulty modifier, I often choose my favorite traits:
- Farmer: For my particular playstyle I guess booze baron might be better but I want a diversified economy
- Hotel corporate buyout: I noticed that an early hotel+tourist attraction counteracts the monthly decrease due to wages and helps stabilize the treasury, instead of it alternating between positive and negative so for example you won't find yourself debt at the crucial moment when a factory needs to import raw materials to be unloaded from a docked freighter
- Financial genius, entrepreneurial, hardworking: For production and export price bonuses
On the other hand, game settings do affect the difficulty modifier so for
island geography I go for
moderate settings but occasionally for a challenge I set both minerals and vegetation sliders to minimum and import everything and have sort of a mini-Japan going. Also, some pre-made maps come with somewhat higher difficulty modifiers when in fact some of them are even easier than most random maps because fertile croplands and resource deposits are so conveniently placed e.g. Tierra de Veganza
As with game settings,
- Political stability = min: rebels are notoriously stupid and the people are incredibly gullible and easy to please
- World economy = min: the negative modifiers are offset by more production and higher prices from a combination of traits, building upgrades or edicts
- Tourism = min: I don't focus too much on this anyway, I just build tourist accomodations for building variety and for the ability to zoom in close to the scantily-clad female tourists at the beach sites

Game length =
max: I really feel this and the following two settings' effects on the difficulty modifier do not scale very well; in the case of this setting for example changing game length by +-10 years changes the difficulty modifier by a linear scaling factor of only +-5%, while the main components of score such as population and treasury balance increase exponentially over the course of a game
Starting pop =
min: low starting pop can be grown quite easily by building an immigration office @ open doors, then later by issuing china dev't aid and festival of love as well as building hospitals/sanitaria @ "obstetrics" work mode
random events =
normal: I've often considered setting this to the max because most of them are readily solved with money when the economy is established but if you're unlucky enough to get one at the very start of the game it could be game-breaking.
And finally,
Rebel yell + free elections =
on: as I've said, rebels are notoriously stupid and the people are incredibly gullible and easy to please, and if ever election results are in doubt just issue a tax cut right before the results come out
Faraway place =
on: tourists still come, some ironically from places that are further away from the US, if we assume Tropico is located somewhere in the caribbean, which is directly to the southeast of the US
Given these settings, and especially the new modern times cheesiness, my games turn out pretty well, as evidenced by
this little snapshot from my current sandbox game: agro-industry fueled by bio-farms is maturing and am currently expanding into mineral deposits to feed my weapons/jewelry factories and later electronics and car factories... onward, my malnourished underpaid and overworked slaves!
...
(P.S. holy hell I think I got a bit too carried away there!

Gonna get some sleep now)