With a show like this, where you never know all of what's happening, we don't really have enough info to answer the question, but are there any nominees?
Sawyer's hair after the first couple episodes is definately a nit, but hardly a major one.
Like Hurley's weight? We discussed that in the "Premises" thread right above this one.
I think that all or most episodes have nits that people point out, as is the case with most TV shows and movies that we talk about on this site.
Hurley's weight has been addressed. Whether it's believable is another matter. But I'm talking about major nits, things that seriously contradict other episodes in such a way that both explanations cannot possibly co-exist, things beyond the 'tv show convention' perimeter.
I haven't seen any ICBN's (look it up in the Glossary) so far. But there's a lot of stuff that still needs explaining.
Yeah, no major contradictions so far and nothing on the scale of Voyager's Cabinet of Endless Shuttles.
Remaining unknowns from Seasons 1 and 2 that I can think of:
1. Kate's horse
2. Shannon's visions of Walt
3. The smoke creature
These are not nits, just unknowns.
Other remaining unknowns:
What the Others want/need with children
More non-nit unknowns:
1. What is the signifiance of the cursed numbers?
2. Why do they figure prominently into everything that has happened to our lostaways?
3. Why is everyone part of "6 Degrees of Lost"
4. SPOILER for 10/18 (highlight): Locke's visions
And of course, the biggest unknown of all: why can't ScottN spell "significance"? 
ScottN: 1. What is the signifiance of the cursed numbers?
2. Why do they figure prominently into everything that has happened to our lostaways?
I'm not sure they actually will ever answer that on the show itself. They in fact already did so in that Lost Experience finale. If anyone wants to see it, links are in the Numbers thread and the Theories and Speculations thread.
There are still plenty of unknowns left on the show. In fact, after I bought the Season 2 DVDs, I started adding little "Unanswered Questions" to my notes in the episode summaries. A few I can think of off of the top of my head...
1) Anything involving Christian Shephard on the island, including the visions, his voice in the speaker, and his empty coffin.
2) The two corpses discovered by the caves.
3) The black and white rocks and any of the black and white symbols.
4) And that statue. THERE ARE FOUR TOES!!!!
The four toes are quite easy to explain. The statue was created by a Disney animator.