Some basic/intermediate stuff:
Smugglers, more than most gainers, gets a boost from scaling TfB. When you can Apprentice or Salvage cards you don't want (say early duchies), it adds a lot of flexibility. The Remodel family does double duty - it allows you to get rid of cards that don't fit your engine and it increases the odds that the opponent with have useful $2- 6 gains.
Potion cards tend to really hurt opening Smugglers and may contradict them the entire game. For instance, Apothecary will mean a lot of dead Smuggler draws while Golem will mean some dead draws and a lot of danger with mandatory, specified gains. Now Smugglers can be more useful mid-game (e.g. when Pool tends to be gaining lots of actions or recovering from Familiar cursing might make playing the Smuggler lottery a valid choice), but early turns with dead Smugglers are pretty harsh. The one exception tends to be Vineyards where folks tend to want to gain a lot of actions early and where you virtually never lose a Vineyard buy for having gone Smugglers.
I've heard folks say that $7 or $8 cards makes for bad Smugglers. In my experience this isn't so. Forge, Kc, and Expand all can get a lot of use out of Smuggler (granted Kc can be a bit of crapshoot, but Smuggling $15 worth of cards even once is pretty nice) and with Forge/Expand you can always trash your Smugglers. Peddlers are a bit iffy, normally Smugglers isn't a great enabler (terminal, non-drawing actions being weak at mass gaining Peddlers) ... but if there is a card your opponent prefers to Peddler at $4 (e.g. a Wv over a $4 Peddler) it isn't so bad. Prince of Smugglers is pretty lousy, far better to Prince something that lets you draw and play your Smugglers; however Prince decks almost always revolve around getting through a lot of your deck each turn (engine or sifting) and Smugglers can work alright at building up engines.
General stuff:
The big question is the opportunity cost. Smugglers will turn a lot of turns that would have been $5 into a $3 + Smuggle and less commonly but still important you will have a number of early $2 + Smuggler (while $4 ain't $5, $2 cards may not even be out). If your Smuggles are useful $5s you just got a free village, nice but how often are they going to be $5 and useful?
If your opponent opens Silver/Silver you have an have an 8.8% chance of both of you missing $5 in the opening. You also have a 14.9% chance that your opponent will hit $5 both turns again, you come out netting a free village. But on the rest of the time your opponent will likely have a $5 one turn and a $3 or $4 the other. You will only line up a single Smuggler half the time (assuming you go second), so half the time you will get $5, $3, X and the other half the time you will get $3, $4, X. The math can be known to be better or worse for P1 as T1 tells them what cash value they can expect for a Smuggler hit on T3.
But this assumes the opponent is going Silvers. Presumably there is a decent terminal (either +cards, trashing, curser, or +$/attack) in most games. If the opponent opens with non-TfB trashing your Smugglers face big odds of hitting $2s or nothing. If the opponent has gotten a Swindler, you might want reconsider adding $5s (particularly if you are trashing) when they might turn into Duchies. +cards gives your opponent a cycling advantage early and that can be enough for them to come out ahead with a T3/4/5 buy of Smugglers themselves (particularly if that means you end up smuggling Smugglers and get off whack on action balance). When to buy Smugglers, assuming it is indeed viable, depends a lot on how the opening turns will go. Ideally you want your opponent to be gaining a lot of versatile cards (+cards, and +action) and a lot of high cost/power cards ($5 & $6) before you dip into Smugglers.
In virtually every engine match-up Smugglers eventually is useful for some amount of time. That time is when Smugglers is very likely to be a live card that gains something worth busting a $5 buy. It also tends to become unuseful for a time - when buys are $8, $9, or $11 and then may become useful again for Duchies, spare card gains (e.g. opponent buys Province/Warehouse), or pile threats. You can make a pretty decent educated guess based on just the board and a VERY good read if you can anticipate your opponent of when you want your Smugglers. Don't get it too early (e.g. T1 in a Familiar game) nor too late (e.g. a turn or two before the opponent will start reliable province buys).
Against an opponent who is good at tracking your deck, expect both the early and late dead periods for Smuggler to be longer. You can significantly hamper Smugglers by timing types of buys (e.g. if Bazaar/Council Room is the engine build then it can be worth it to muck up your own action balance a bit to ensure that your opponent gets starved for Bazaars, particularly if you can double tap Bazaar once when they are unlike to Smuggle and again to pile out at something like 7:3 or 6:4).
