By default, skill 1 on all weapon sets is set to auto-attack. To toggle the auto-attack status of a skill,+ Right-click that skill. Only one skill at a time can have auto-attack status, so enabling auto-attack on a different skill will disable auto-attack on any other skill. Note that some skills, most notably any that are ground-targeted, cannot be set to auto-attack.
Manually activated skills take priority over the auto-activation skill, within the time limits of what the skill animation allows for . As soon as the manually activated skill has been executed, the skill that's on auto-activation will activate after the animation of the manual skill has ended (if it meanwhile has recharged).
Targeted auto-attack skills will continue to activate against the original target even if you select a different target. To disable this feature, open the options panel, and under Interactions choose "Stop attacking on target change."