For me (as a beginner), I've found the combo of Joe Diamond and Mandy Thompson pretty lethal (as 2 of a quartet).
If you tend to combine Joe and Mandy's personal skills, Joe becomes almost undefeatable. For spending one clue-token, he essentially gets four re-rolls. (often more if e.g. he's rolling 5 dice and you use Mandy's skill before spending a clue token).
So far, we've played with 2 players using 2 investigators each (Joe, Mandy, Jenny and Pete). Joe mops up Arkham, Jenny goes to the bank then the curiosity shoppe to get cool items, Mandy swiftly closes 2 gets and we use Pete as a fairly versatile extra (gate sealing if thinsg aren't too hectic in Arkham, helping mop up monsters in Arkham if needed).
Once we were able to use monster trophies and gate tokens to bless the party, it seemed like pretty plain sailing. Certainly, once 3 gates are sealed, it felt hard to lose.
So far, to my great surprise, we are 2 and 0 (beat Azathoth with doom track on 10 and Ithaqua with doom track on 8).
No obvious spell casters in our team - but this didn't seem to hinder us too badly.