I started with corn. Made a few gens, then started to add more rye instead of corn as replacement grain (I replace like 25% of the grain each generation). I did the same with barley. Then I decided (since my corn over here doesn't give much taste) to try and do an all broken barley. I used some 25% backset of the latest corn/barley combo. I made some 4 gens of that and liked it. Next thing is I switched to all rye. I used the last backset of the all barley to start that up. First two gens were pretty good already, but from gen 3 it really gets well. If I change my recipe, I usually use the first two generations for a vodka, and from gen 3 I start to double pot distill it into a whiskey.
Now that was the long answer. Now the short one: no, I never do a one off. Always at least 4 generations.
Say I have like a few kilo's left of something (had some 5 kilo's of peated barley malt for instance), and when it is not enough to start making continuous generations with grain replacement, I just dump in what I have (5 kilo's in this case) and make 4 gens not replacing grains. My feeling is the grain can get you 4 gens without replacing and taste only gets better. After that, you really need to replace grain to keep up the taste profile. If I have a lot of a certain grain, I simply replace 25% each time.
Try to find your taste, what you like! If you think your corn is too sweet to your palate, maybe add some rye or barley. Maybe malted. Or spelt or wheat. It is the experimenting I love. For me rye gave me the best. And then I "upped" to all malted rye ... and so far it is not good. Well, gen 1 wasn't. Gen 2 will be distilled this weekend. Who knows?