The Rattlesnake is currently considered the king of PvE, and for good reason. Firstly, the dual bonus to damage of thermal/kinetic missiles and drones means that it can apply high amounts of DPS from a distance. Secondly, the high base stats mean that it can have a very respectable tank. Lastly, the recent drop in price means that they are very affordable — comparable in price to the various navy issue hulls.
It is most effective against factions that are weak to kinetic or thermal damage.
I use this fit against Guristas pirates. (o.smium link)
It requires relatively high skills in at least two of shields, drones and missiles to be used effectively. It also requires high capacitor skills to run cap-stable. In my case, I have high shield, capacitor and drone skills, but absolute shit missile skills. This is very much reflected in my DPS. Instead of the just under 1200DPS @ 108km maximum that a full t2, max skill fit would give me, I’m making do with just under 800DPS @ 105km. However, this is still greater than any other fit I can currently fly.
The optimal way to run Sanctums in this fit is to warp in at 0, drop your MTU if you use one, then use the microjumpdrive to get to the engagement position, the location of which is beautifully illustrated in the skillfully drawn diagram below.
The engagement position should, ideally, be in line with the middle ring of the Sanctum (only ever run the ring variants – the other variant gives less bounty and takes longer to complete because there is lots of ECM/sensor dampening). However, anywhere roughly around that area will do. Just make sure you are in range.
Putting 100km between the rats and yourself serves two purposes. Firstly, you will be out of range of the smaller ships, and be able to kill them before they can get in range. In Serpentis sites, you will also be out of range of all the blaster-fit battleship rats. This means you don’t need to tank as hard or worry about being pointed/scrammed/webbed by the frigates. Secondly, it will give you a couple of extra minutes to react to hotdroppers who come into your system — assuming you’re watching your intel and local channels.
Which leads nicely into the second topic of this post — WATCH YOUR FUCKING INTEL AND LOCAL CHANNELS. DO NOT RAT AFK. It’s not difficult. There is plenty of time to react to neutrals/reds coming into your system, even if you’re sitting in a huge ship in the most prominent anomaly in the system, as long as you’re keeping an eye on your intel and local channels.
AFK ratting might seem like a nice prospect — high, semi-passive income — but in practice you’re a big glaring target to hotdroppers, and will almost invariably end up losing more money than you make. Furthermore, when droppers get kills in a particular system, they tend to hang around that system, which will make your co-inhabitants rather unhappy.
I used to live with a group that would kill blue AFK ratters rather than give droppers a free kill, because an awox looks better on the killboard than a stupid loss. I fully encourage alliances to adopt this attitude.
By all means, run a fit that requires minimal player input, but STAY AT THE KEYBOARD. Every time you leave your keyboard while not cloaked, in a POS or in a station, a puppy dies. You are killing little, innocent puppies. You goddamn monster.
The Omnisphere 
