Simic is a fun guild but tends to have ruther clumsy cards that are hard to place in many archetypes. Overall it is one of the most powerful, if not the most powerful, of all the guilds containing blue. Simic is probably also superior to Boros and Rakdos in terms of depth and average playable card quality. Here is my top ten Simic cards for cube play:
Mystic Snake is a lot worse of a Counterspell than Plasm Capture as a mana injection tends to be more use than a 2/2. The G / 1 casting cost difference does mean you have to be careful about other colours or colourless land but overall they are both a bit of a pain to cast. The reason that Mystic Snake is so much more played than Plasm Capture is that it is a creature card and thus has loads of synergy with other cards that no other counterspell has. You can create very easy soft locks with cards like Waterfront Bouncer and Crystal Shard in combination with Snake. You can tutor is up with Survival of the Fittest, you can Aether Vial it out for free and without risk of being countered and so on. As we know, four is a lot to keep up and is really rather obvious so you find a lot of the time that you will just counter the first thing that you can with it. Although a 2/2 is nothing to get excited about it does mean you get a 2 for 1 as well as an injection of tempo. Typically the decks that play Snake are more tempo focused and have lots of creature synergy using cards like Opposition all of which improve the value of a 2/2 body. The fact that Duress, Negate, Spell Pierce etc all miss it is also very satisfying!
Simic Sky Swallower remains one of those best in slot cards despite actually being fairly underpowered compared to what seven mana affords these days. On paper you would think Sphinx of Jwar Isle was largely more playable being only one colour and costing 6 for a 5/5 rather than 7 for a 6/6. Trample is certainly better than looking at the top of your library most of the time but is much more important for a 6/6 than a 5/5 and with flying already it is no significant loss. They even have the same clock to kill from 20 life. Despite this the Swallower is used as a threat in Simic ramp decks and as a card to cheat into play with Oath, Natural Order, Reanimate and even Show and Tell. Few cards indeed manage such a feat as to be worth cheating out but also castable in the normal manner. Sky Swallower just gets it done, it is very hard to kill and just keeps sending in damage. It is just the right blend of hard to block, quick to kill with and awkward to deal with to be frequently played in a much wider range of decks than almost any other seven drop (with the exception of Karn Liberated presently). It is not an exciting or fun card like Griselbrand or Elesh Norn but then simple and to the point are usually the traits of the best and most played magic cards.
Trygon Predator is a royal pain in the arse. Most decks have targets for him to eat up and even those few that don't still don't much like 2/3 fliers. Once made there is usually a mad panic to find a way of dealing with him, if that fails you then start to lose tempo and card advantage as well as being highly restricted in what plays you can make. While you automatically assume he is killing artifacts and enchantments he is just as useful at dealing with planeswalkers. There are precious few 3 mana or less cards that have flying which are cube viable and fewer still that have all round robust bodies. As such you can fairly reliably chunk planeswalkers for two in the mid game with a Predator which stops them from being cast or at least stops them doing much useful. There have been so many games in which I am either throwing down sacrifical planeswalkers to try and stop them eating my other cards or throwing out artifacts and enchantments in the hope that they will be tempted to destroy them rather than attacking my planeswalker. I do find it a little hard to include Predator in lists because I don't know how good he is going to be if I don't know what decks/cards I will be facing. When you know you have important things to kill you play more reliable quicker removal like Nature's Claim because you cannot risk giving them that extra turn of use of just Bolting your Predator before it does anything for you. Even so, whenever I do find room for this little man I am never disappointed. It sure don't look like it can fly but then I guess physics is less relevant where magic is concerned.
Edric, Spymaster of Trest is less effective than Trygon Predator and should perhaps be below it in the list. A large part of this is how obviously powerful he is meaning people are more prepared for him and usually stop him doing anything much at all. Edric rather relies on you having a good position in which to use him and a lot of the time is just a win more card. If you already have a couple of attackers getting through then chances are the game is yours. If not you are paying three mana for a 2/2 and feeling sad about it. While he may be wildly inconsistent he is a very cheap way to draw a lot of cards in the right deck and is hard to pass up as a result. He will typically eat the first removal spell your opponent can cast once he hits the board which is not what you want to happen but also not a disaster. Although swarmy token decks and elf decks do work decently with him you are very vulnerable to mass removal. My preferred type of deck for Edric is a tricksy tempo deck, often with Opposition as a finisher, and which has a high concentration of cheap evasive dorks that do other things as well such as Looter il-Kor, Trygon Predator, Kira, Great Glass-Spinner, Blinkmoth Nexus, Strangleroot Geist etc. Edric is a very very powerful card that relies upon support, position, design and planning to realise that power. He is also fairly broad unlike a lot of the more interesting cards for deck design and so while he is not a must have for a cube he is a good way to make things more complex and interesting. You are also hard pressed to to find a cheaper way in which to draw a tonne of cards without costing you some other resource or giving your opponents cards too.
Shardless Agent is a lovely card that I rate above Bloodbraid Elf, although only just. It is a very cheap tempo and card advantage dork that has a wide range of applications. Agent offers more consistent returns on the cascade and is less restrictive on your construction than Bloodbraid. It is also cheaper so you can put it to use earlier. Another thing in its favour is that it is more generic than Bloodbraid Elf and therefore fits cleanly into a wider range of strategies. Of all the cards that stand out in cube, those creatures that offer both tempo and card advantage simultaneously are a significant proportion. Those that are on the cheaper end of the spectrum are played whenever the opportunity present and as they are viable in aggro and control strategies so that opportunity is often. Shardless Agent is one of the least played of that elite group although it is far from the worst. It is because there are not that many UG archetpyes, many of those combo, and so the Agent is not always suitable. On top of this it makes two or fewer mana counter magic unwise to play which is a fairly big part of many blue strategies. The more redundant your deck, or at least the potential cascade targets, the better Agent will be for you. It will only ever be bad for you if you have miss built your deck in regards the Agent. All in all it is a very cheap two for one that should provide that advantage in a way desirable to your deck rather than things like Trinket Mage or Stoneforge Mystic which require you to includes certain other cards to do their thing and so you build around them rather than Agent who works with you to do what you are trying to do. Another perk of cascade cards is that they force through the 2 for 1 unlike Eternal Witness and other enter the battlefield effects when facing counter magic. Final point of note is that Agent is an artifact which increases his potential synergies while not being an issue in regards increase susceptibility to removal as you don't overly care about the body once you have cast it. Trading an in play Agent for a Disenchant or similar makes you feel even more ahead.
Lastly we have some honourable mentions for those cards that have been played but seldom or just the once.
Prophet of Kruphix
The Coatle is looking rather outclassed by Chasm Skulker these days and is likely already enjoying an unknown early retirement. There are plenty of powerful midrange dorks that suffer from lack of archetypes in Simic, there are also some cute smaller dorks with nice effects but that never seem to be enough to make a final 40 list. Simic is one of the guilds that has a flavour that is most removed from what that colour pairing tends to want to be doing in the cube. Those cards that do have overlap in this way tend to be outclassed by the more direct mono colour offering. If you want to ramp then the green options typically outclass the Simic ones, if you want to draw cards or counter spells then it is the mono blue cards that are top of the pick list. Powerful cards but hard to use well and so Simic cards are among the least played gold offering in cube.