Keep track straight — Avoid tight turns.

Put signals close to points — The points will be freed up earlier.

Keep signals 2-4 tiles apart — Too much space between signals forces trains to space out unnecessarily. Too little space makes it hard for blocked trains to reverse.

Bridges 4-5 tiles long — No signalling is possible on bridges (currently), so longer ones cause more inter-train spacing. Bridges 3 tiles long use only the basic technology, which reduces the maximum train speed.

Tunnels 3-5 tiles long — Similarly, no signalling is permitted in tunnels, so keep them short.

Replicate long bridges and tunnels — If you must use long bridges or tunnels, create parallel replicas, and use pre-signals to evenly distribute traffic between them.

In junctions, split track before joining — If tracks from different lines join first, and then split, trains could contend for the same short section of track between the join and the split, even though their paths don't cross anywhere else.

Use pre-signals on entry to stations — Force arriving trains to defer selection of platform until at least one is available.

Use deceleration track when Realistic Vehicle Acceleration is enabled — The extra track allows a train to slow down as it approaches a platform after it has cleared earlier points. Subsequence trains therefore advance sooner.

Use depots as sponges — Escape depots soak up excess trains to prevent queues backing up onto mainlines.

Gather industries producing the same cargo — Build factories, oil refineries, sawmills and printing works close together. They all produce goods, and their output can then be mixed together. Use waypoint-selected platforms, or a separate circuit and short trains to shuttle the goods away to a more central or spacious location (from where you might fly them out) – that avoids bumping into the station-size limit.

Create duplicate or triplicate track — Insert periodic crossovers so that each track acts as redundant for the others. Use junctions that sustain this redundancy.