Here are some ideas on how to adjust the settings. Although this depends very much on each individual the advice is bound to give you some insight in the matter.

Maximum number of competitors: 0
If you're more of a builder than a competitor (against the programs inferior artificial intelligence), opting for no competition allows you to expand your network limited only by your bankbalance, the counsils approval and the effort you put in to it. Any competition tends to get in the way of our grand designs.

Vehicle breakdowns: none
Train breakdowns disrupt the daily business in a big way. Not only will a train be delayed but trains behind the one broken down are stuck as well. Several of those trains will then break down themselves causing mayhem to your operation. This makes it basically impossible to exploit busy lines.
But be aware: Regular (mandatory) service is still neccessary though even if 'vehicle breakdown' is set to none. Because whenever a train is due for service (set with the service interval for every vehicle) it will look for the nearest depot. If that depot isn't on it's route the train is likely to get lost.
With this selection comes another rather welcome advantage. Since the trains will no longer breakdown a reliability percentage of zero percent doesn't affect the train anymore. This means you no longer have to replace old engines on a regular (every 20 years or so) basis. This surely is some kind of cheating but it's just a bonus on an otherwise fair choice. Afterall, the mandatory servicing should keep those engines in the best of condition or we'll sack the maintenance crew! Ofcourse if you're still not happy about it feel free to replace those oldies whenever they're at the end of their lifespan.

Train reversing: at end of line only
This setting makes the use of RoRo-stations possible. Setting this to the other possible value ("at end of line and at stations") causes a train in a RoRo-station to reverse if it'snext destiny is 'behind' it's present position. And reversing in a RoRo-station is of course a contradiction in terms.
{(Also: If you sometimes 'micro-manage' your train, letting it unload before reloading, etc; this is easier to do with 'reverse at end only'. Cecilie)}

Miscellaneous
Now you can concentrate on building an empire. However add a little challenge if you must:
Disasters on (versus off), economy fluctuating (versus steady).
These can be changed after your game has started.

terrain type hilly/mountainous (versus very flat or flat);
'maximum intial loan',
'initial interest rate',
'vehicle running cost'
These influence your game as well, but are fixed when your game is generated.

No harm in experimenting, as long as you keep those trains running!