There are a variety of faster-than-light (FTL) drive systems available in the Samusverse. The great challenge of intergalactic travel is not, then, covering the vast distances between stars in a timely manner, but in actually choosing a path through those same stars that bridges points A and B.
The shortest distance between two points is, of course, a straight line. However, ships rarely take the most direct possible route for two reasons. The first is that most FTL drives, while powerful, cannot be operated safely within the gravitational well of a large stellar body; colliding with a star at superluminal velocities is an ugly, ugly business, and even a near miss can throw a ship off unpredictably. More, stellar gravity wells tend to interfere with the FTL methods most widely available, and the rest produce a heavy radio-wake that makes their use in an inhabited system dangerously callous. Spacefold drives in particular have this problem, and more than one planet was rendered sterile before laws limiting the drives' insystem use were passed.
The second is a simple matter of logistics. A ship must carry enough fuel to power not only its drive, but all systems, for any voyage it may make. It must also carry enough food, water, and air for its crew for that distance, or the means to produce those consumables. A prudent ship must also carry sufficient tools and parts to repair forseeable problems from system fatigue, and enough arms and armor to defend itself (at speed, debris can be as dangerous as a dreadnaught). A longer trip demands more consumables, which need to be moved by a larger drive core, which requires a larger powerplant, which needs more fuel. The longer the distance, the more the problem compounds itself, and only the most massive ships have the self-sufficiency to cross the galaxy without a stop.
As a result, most ships zigzag from star to star, with the majority of travel time spent on subluminal travel between entry-point and exit-point in a star system. Systems rich in resources or sitting along a safe corridor through otherwise cluttered space become major travel hubs as a result. Also likely to become major stopover ports are those stars gathered in small clusters above or below the main body of the galactic disc. From their position outside the main bulk of the galaxy, they offer straight, unobstructed headings to literally millions of star systems.
There is one final complication in interstellar travel that must be considered in plotting a course: stars, nebulae, major comets, and the like are in constant motion. It is not enough to plot a course that avoids where dangerous objects currently are, one must plot a course that avoids where they are going to be.