While some folks focus on "specializing" in one game or variation (6max, FR, HU, etc), I'm finding better success by mixing it up.
For example, I crushed HU at 10NL banking a very significant (and in my opinion, unsustainable) winrate of 47.38 bb/100 over approx 5k hands. This swelled my bankroll so I started taking shots at 25NL HU.
And got crushed for about 8 buy-ins at that level. Played poorly, ran worse, tilted a bit for the first time in a while, and finally did not table select well (by choice to some degree as I wanted to challenge myself to get better by playing against regulars/better players).
And although I lost money, I think the experience far outweighs the negative impact on my bankroll.
So I took a short break from HU to play some 6max. And crushed it over a small sample size, winning back a majority of my losses at HU. The game just seemed soooo much slower. My understanding of opponent's hand ranges, player types, etc. were much much more accurate. I'm extracting good value from my big hands and my not so good hands.
So after a couple days of 6max, I decided to play some FR. Ridiculous how soft these games are. Utilizing a much improved understanding of player type, table dynamics, knowing what my own image is, I'm finding a huge amount of success at the FR games. I think with so many training sites having such a big focus on HU and 6max, that you now have 2 types of FR players: the super NITs that mass multi table and are exceptionally exploitable and then the casino donks - those that play FR at the casinos and then decide to try online (play 50%+ of hands for example).
For example, tonight I ran pretty hot playing a whopping 4 tables of FR winning 6 buy-ins in 1.5 hours and 360 hands. While, yes, I ran very hot; I also exploited the hell out of my opponents with my big hands getting them to commit their stacks to me.
For example, I tilted one player by continously attacking when he showed weakness. He decided that he was going to make a stand for 65 bbs by 4bet shoving AJo over another one of my 3bets. He ran into my AKs. After reloading, he slams AQo by raising 6x PFR, I flat. KQx flop, he pots it and shoves over my minraise. Whoopsie. My AK has him crushed; he curses a bit, reloads again and sucks out on someone else for a stack. His tilt fades and I avoid giving any of my stack back to him.
Oh well, starting to ramble. With a bankroll over the 1k mark, I'll probably mix some HU back in as I continue to flip between soft games at 6max and FR. Good luck to all of you out there.
And seriously consider playing some HU just for the experience.
PS -> It will also help your tilt control! More on that later.