Flyback Voltage Feedback Quality
Load regulation will tend to be much worse with transformer feedback because the windings are not perfectly coupled - there is leakage inductance in a real transformer. This can be minimized by keeping the feedback and secondary windings as close as possible but there are limits to that since galvanic isolation depends on the insulation between the two windings. To put it bluntly, if the wires short, people could die.

The voltage across the output rectifier diode(s) will also increase with increasing load current and the average voltage across the filter caps will decrease a bit, and there will be drop due to non-zero output winding resistance. None of these changes occur in the feedback winding so they will not be automatically compensated. 

You can see these effects in DC-DC converters where only one output is regulated, an loading the regulated output causes the other outputs to increase in voltage. With minimum loads applied this can be tolerable, but it is very noticeable. It really is a cross regulation thing- the feedback winding is another (lightly loaded) output that happens to be tied to the primary side.

It may be possible to (partially) compensate for these factors by fiddling the feedback a bit with increasing primary current, and I believe some controllers adopt this strategy to avoid the opto. Another approach is to follow the poorly regulated output with an LDO linear regulator.