The galaxy in EVE Online is vast. This provides a huge space in which gamers can pursue their goals of market dominance and PvP, but the downside is it can take a long time to reach other regions. For high sec runs, autopilot can be your friend. But always be careful that your plotted course doesn't take you through lowsec space. There's nothing worse than coming back from being AFK and finding your ship and pod have been blown up in lowsec while you weren't watching. It goes without saying that using autopilot in 0.0 space is tantamount to suicide.
In the event you break the first Commandment, you will hopefully have obeyed the second, which is to ensure your clone is up to date and your ship is adequately insured.
Having a good overview setup, with tabs for each type of situation you're likely to face, allows you to assess your situation and react quickly. Using the overview is essential in virtually all activities players engage in outside of a station, but when it's too cluttered it just causes frustration. Knowing the basics of overview setups and more advanced uses will greatly improve your effectiveness as a pilot in EVE.
Lazy highsec mission runners flying battleships sometimes use smartbombs to deal with frigates or fast moving rogue drones. While it saves time, this area-of-effect tactic will have a tragic result if an uninvited guest warps in on you or you otherwise catch someone or something with your smartbomb that triggers CONCORD. ECM burst effects in highsec, particularly outside stations, are also ill-advised. Smartbombs in highsec... isn't very smart.
Every ship has a weak spot in terms of resists, some moreso than others. If you're flying into a mission, you need to know what type of damage to tank. If the damage dealt by NPCs and especially player characters is aimed at your shield or armor weakness... it's like being kicked in the sack. Tank accordingly.
It would seem that if you shield tanked AND armor tanked at once, you'd be pretty much invulnerable. Sorry, but that's an illusion. Sacrificing mid slots as well as low slots in your ship setup gimps you in substantial ways. Shield tankers need their low slots for damage mods, or simply to help support their tank. Armor tankers need their mid slots for electronic warfare and propulsion mods. Choose to either shield tank or armor tank, not both.
Watch your Local channel at all times while in lowsec or 0.0. This simple bit of vigilance will ensure that you're not taken by surprise while you're carrying on with your business ratting, mining, or mission running in any space unprotected by CONCORD. Many players detach the Local channel from their others and keep it on screen, so if Local spikes with hostiles they have time to react. Namely, by warping to a safespot...
Safespots are essential to survival in lowsec and 0.0 if you plan to spend any length of time in a given solar system, and especially if you're flying solo. Having safespots in highsec systems you're based in are also essential if you're at war with another corporation or alliance. Safespots are not hard to create, but it does take some time to get the hang of creating non inline safespots. That is to say, creating bookmarks that fall outside of the warp path between celestial objects. Check out Goonfleet's guide to safespotting for a comprehensive how-to.
One of the distinguishing features of EVE is its time-based skill advancement. So you're always moving ahead, whether you're logged in or on vacation. Still, with the vast array of skill paths you can take, and their numerous prerequisites, creating an optimal skill plan in your head or even on paper can be a challenge. That's where EVEMon comes in. It's a free program that lets you choose a ship, a module, item, or most whatever you want to have or do in EVE. Then, EVEMon will create optimized skill plans that allow you to reach your goals in the shortest amount of time. EVEMon is one of those must-have programs that all EVE players should use. But only download it from its official source at BattleClinic.
No matter how long you've played, there are aspects of the game you've not fully experienced, or have changed since back in the day. Most every EVE player, at some point, has felt confused or daunted. A game with this level of depth and complexity coupled with the ever evolving nature of an MMO ensures that there's always something new to do, learn, or explore. Don't be afraid of messing up. We all do at some point. Just do your best to learn from your mistakes, and you'll emerge stronger and smarter.