If you only have the second best possible hand according to the board, then there is a very good chance that you will get beat by the best possible hand. Play for the nuts. Second nuts can get you in trouble.
The nut straight on the flop isn't really that great if there is a higher straight draw possible, and you don't have a redraw for it. Or if you have the nut straight on the flop, and there is a flush draw possible of which you don't have the draw for.
Summary: Play for the NUTS!!!
Naked Aces aren't worth a damn. By naked, I mean pocket aces, not suited, with two cards that aren't connected to each other or the aces. With naked aces, you are generally going to need to hit an ace, and you still might lose even if you hit an ace. You have to get to heads up with that hand before you are even favored to win. With 3 players, you would only be at 45% to win. Even with the best Omaha hand of AAKK double suited, you are only favored at 54% with 3 players, but at 71% with 2 players. On a table with lose players and/or smaller stakes, you probably aren't going to be able to isolate to heads up in PLO. Every time I play, during the night I will see quite a few pots, repot, repots, that end up 3+ players going all in preflop. Many go in with what I would basically call "trash" hands. Unlike holdem, the best preflop hands lose more often.
Summary: Don't overvalue Aces.
A strong hand in holdem is probably not as strong a hand in PLO. The chances of hitting two pair on the flop in holdem is 2%. The chances of hitting two pair in PLO is 10%. If you hit two pair on the flop, you really want it to be the top two, and not the bottom two. Also, two pair with a straight and/or flush draw on the board, makes your hand even weaker unless you actually pair the board and/or a straight card doesn't come. If there is already a possible straight on the flop, then your hand is even weaker and you are probably going to need to catch up by hitting one of your 4 outers.
If you hit a set, it is a strong hand, but still not as strong as a set in holdem. If it is a bottom set, then it is in danger of getting beat by a higher set. Unless there were some big preflop bets, it is probably going to be hard to get flush draws, straight draws, or top two pair out of the hand. And if top two hits, you are going to hit your full house and still lose. Full house beat by higher full house happens way more often in PLO than in holdem. Also, if you hit your set on a board where a flush or straight is already possible, you are probably going to have to catch up and pair the board. On the plus side though, a non nut flush or straight with no pairs or redraws is likely to fold if you pot with your set on the flop.
Summary: Don't overvalue your hand post flop. The nuts can change with every street.
You want your preflop hand to have range. Pocket pair, double suited, with connectors, is my idea hand. With that hand you could hit a set, with a straight or straight draw, and a flush or flush draw. You can even hit a double flush draw on the turn. Some people are partial to double suited run down hands. That can give you wraps or straights with redraws for the higher straight as well as flush draws. Now getting these types of hands exactly are rare, and if you played those hands exclusively, then it would be as boring as playing holdem. However, the closer you can get to that range of hands, the better. The greater your range, the less chance of your made hand on the flop getting beat by a better hand on the turn or river.
Summary: Play hands with range to give you multiple draws or hits on the flop.
This probably over complicates things, but I just have to mention it. The rule of 4/2 to determine your
odds of hitting on the turn and river is a great tool. I go by it all the time. However, because everyone gets 4 cards in Omaha, if you are playing a full table of 8 or 9 people, then you need to keep in mind that 70 to 75% of the deck is dealt out by the flop. So you hit a flop with a full wrap and a flush draw and think "GREAT I have over 20 outs." You need to take a reality check. With a table of 8 players there are only 17 cards left after the flop. With a table of 9 players, there are only 13 cards left in the deck after the flop!! So there is a higher chance that your "outs" were already dealt to someone else than there is at a holdem table with the same number of players.
Summary: You don't really have as many outs as you think you do.
Also, if you have a pocket pair that is needed to make a straight, don't assume that because you have the "blockers", that there is little chance someone doesn't have that card to make that straight. The majority of the cards have been dealt preflop, so there is a good chance someone in fact DOES have those cards. Heck, I had a hand of TTT7, which is a bad hand you should actually fold, but there were no preflop raises and it takes a T or 5 to make a straight, so if I hit a straight I have "blockers" and will probably be the only one with the straight. I hit a 986 rainbow flop. Nut straight, and I am thinking it is unlikely anyone has the higher straight draw because I have the "blockers". I bet, one guy calls. Turn comes and it is a blank. No pair, still a rainbow. I pot again. Guy calls. River comes and it is a seven. I pot. He repots. I am thinking "No ****ing way!" I call. He has a JT and the nut straight.
Summary: With the majority of the deck being dealt preflop, there is a greater chance that that "blocker" is actually in one of your opponents hand.
I can think of a lot more things to input, but I don't want to write a book here. LOL.