No single site is best for everything, so it depends on, what you are looking for. It also depends on your location, since many sites dont offer their services everywhere. But if they are available, then you cant go to wrong by sticking with the sites, that have been around for decades, and have aquired licenses in many regulated markets. These include:
* PokerStars (HUDs allowed)
* PartyPoker (HUDs not allowed)
* 888 Poker (HUDs allowed)
If its available I would also consider giving this a chance:
* GG Poker (Build in HUD, no external HUDs allowed)
GG poker have emerged as the main competitor to PokerStars and seem to be moving in the right direction by getting licensed in at least some markets. As for the rest they are basically unregulated (illegal) sites, and I would only choose them, if the regulated sites are not available.
Its never going to be quite as safe depositing or playing on unregulated sites, and you can read many horror stories in the forum from people, who failed to read, what was written with small print, before they deposited on some new small site, they found on the internet. But among the unregulated options, I would consider the following to be the most trustworthy or maybe its better to say least un-trustworthy:
* ACR (HUDs allowed)
* BetOnline (HUDs allowed)
* Ignition (HUDs not allowed)
* Bovada (Anonymous tables but HUDs providing in session stats are allowed)