If you want to run uniflow you have to plug the overflow, by definition it employs only one vent...which should terminate at the outboard side of the tank, close to the fuel pickup, the idea being it stays submerged and "bubbles" the vent air into the tank. Supposed to give more consistent runs without the typical leaning out as fuel is burnt off. It does work.
With a standard two-vent tank, the vent tubes are usually on the inboard side, clear of fuel, plugging one is unnecessary but probably doesn't make any difference. You will likely notice it leaning out as the flight progresses.
I'm using unifow tanks with my 1/2As and getting much more consistent runs throughout. I built one with the vent tube bent into the slipstream but it richened up too much in flight so I went back to jutting straight out. The only other fuel system that approaches the performance of a uniflow setup for me is, surprisingly (at least to me), the floppy-balloon tanks I sometimes use. They are unvented and collapse as fuel is consumed. I suppose there's a similar principle at work but I can't envision it clearly.
That's all I know about tanks. Well, except pressure, that's another story.
--Ray