3. Wolfram and Hart (Angel)
Wolfram and Hart would be the most difficult opponent for the Doctor on this list, undoubtedly. The company deals in power play, utilising powerful demons and magic users to defeat its foes - and falling back on the Senior Partners if need be - but they've
never dealt with anyone as clever as the Doctor. Having dealt with the Daleks on numerous occasions, even a global (and very powerful and evil) corporation such as Wolfram and Hart shouldn't pose much of a threat to the Doctor. He'd need to do his research but, given that he has a TARDIS to take him anywhere (or any time) that he needs to go, that shouldn't be an issue. And I can see the Doctor simply sealing all the connections to other dimensions that Wolfram and Hart require to operate fully, taking the Senior Partners out of the equation. It's not as though he hasn't done that before. It might be time consuming to fully bring Wolfram and Hart to a close, because of the sheer size of the organisation and their ability to re-staff very quickly, but no single individual within the company is in the Doctor's league. He'd pick them apart like vultures do a corpse.