Ticket to Ride rewards two things: completing destination tickets and claiming long routes. Beginners chase the longest routes for the points-per-card payoff. Veterans chase bottlenecks.
A bottleneck is any single-track segment that only has one or two parallel routes connecting major cities. On the USA board, watch routes through Helena and Duluth. On the Europe board, watch the tunnels between Frankfurt, München, and Wien. Whoever locks these down forces every other player to take a much longer way around.
Draw extra destination tickets aggressively in the mid-game. Most players draw once at the start and never again. If you take a second batch of three when your network already covers most of the map, you'll usually complete one for free and pick up 10–20 unexpected points.
The wildcard locomotives are the single most-fought-over resource. If you see one face-up, take it — even if you didn't need it yet. Denying a wildcard to an opponent can delay them a full turn.