Always right click to attack, never left click.
When selecting different character/group for next command, PAUSE (at least while your game camera shifts viewpoint).
Quicksave often (after every fight even): there's no reason not to, and the game can hang or crash (apart from anything else, my electricity company inflicted a power cut on me once).
A good place for a specfic (named) Save is before you shop, or have a chance to recruit characters (in case you want to go back and see what would have happened if you'd made a different choice). For example, when you enter Stonebridge - the game's own Autosave when leaving town is too late.
Assuming you are running fullscreen (and I don't remember if you have the choice not to) then you don't want any interruption from Windows (like a message saying your weekly anti-Spyware scan is starting) - so shut down your internet and disable every automatic schedule you can find.
If you are not trying to post a fast finishing time, then packmules can be safely left behind in an area you've already cleared out (call it a camp site).
If completing a (journal) Quest or opening a door depends on killing a specific monster, then be careful what weapons you use. If you use a weapon that can freeze, and a victim dies whilst frozen, then that victim simply disappears with none of the expected death effects such as a corpse drop, or an explosion of body parts (treasure does drop normally). This may account for many of the cases I've read about - and had happen to me - when the creature has been killed but the Quest remains uncompleted or the door jammed. This particularly applies to LoA where its stunning etc weapons have the same problem.
Have fun, Richard