Recently I have read two different proposals for a notion of homotopy between functors, and I am curious which contexts each best lend themselves to. The first comes from Ming-Jung Lee's 1972 paper Homotopy for Functors, definition 6:

If $\mathcal{C}$ and $\mathcal{D}$ are small categories and $\varphi, \varphi':\mathcal{C}\rightarrow\mathcal{D}$ are covariant functors, we say that $\varphi$ and $\varphi'$ are homotopic (written $\varphi\simeq\varphi'$) if there is a sequence of covariant functors $\varphi_1, ..., \varphi_n:\mathcal{C}\rightarrow\mathcal{D}$ such that $\varphi_1=\varphi$ and $\varphi_n=\varphi'$, and such that for each $i$ there is a natural transformation between $\varphi_i$ and $\varphi_{i+1}$. (Of course the direction of each natural transformation is unspecified.) In the linked paper, Lee associates to each small category $\mathcal{E}$ a simplicial set $M\mathcal{E}$ called its "morphism complex", and proves that the simplicial maps $M\varphi, M\varphi':M\mathcal{C}\rightarrow M\mathcal{D}$ induced by $\varphi$ and $\varphi'$ are homotopic as simplicial maps if $\varphi, \varphi'$ are homotopic as functors (and hence also the induced continuous maps between the geometric realizations of these simplicial sets are homotopic).

A second proposed definition comes from Ronnie Brown in section 6.5 of his book Topology and Groupoids:

Let $\mathbf{I}$ be the tree groupoid on two elements $0$ and $1$. Then if $\mathcal{C}$ and $\mathcal{D}$ are arbitrary categories and $\varphi, \varphi':\mathcal{C}\rightarrow\mathcal{D}$ are covariant functors, we say that $\varphi$ and $\varphi'$ are homotopic (also written $\varphi\simeq\varphi'$) if there is a functor $\Phi:\mathcal{C}\times\mathbf{I}\rightarrow\mathcal{D}$ such that the induced functors $\Phi(\_ , 0), \Phi(\_ , 1):\mathcal{C}\rightarrow\mathcal{D}$ equal $\varphi$ and $\varphi'$ respectively. (Here we abuse notation and denote $\Phi(\_ , id_0)$ and $\Phi(\_ , id_1)$ by $\Phi(\_ , 0)$ and $\Phi(\_ , 1)$.)

The book includes many results employing this definition; for instance, the fundamental groupoid functor $\pi:\mathbf{Top}\rightarrow\mathbf{Grpd}$ preserves homotopy: if $f, g:X\rightarrow Y$ are homotopic continuous maps, then the induced functors $\pi f, \pi g:\pi X\rightarrow\pi Y$ are homotopic as functors.

As another example, consider the "track groupoid" functor $\mathbf{Top}^{op}\times\mathbf{Top}\rightarrow\mathbf{Grpd}$, which takes a pair of spaces $(X, Y)$ to the groupoid $\pi Y^X$ that has as objects the continuous maps $f, g:X\rightarrow Y$ and morphisms the homotopy classes ($\mathrm{rel}$ end maps) of homotopies $F:f\simeq g$. One can show that this functor preserves homotopy in the same sense: if $f, f':Y\rightarrow W$ and $g, g':Z\rightarrow X$ are pairs of homotopic continuous maps, then the induced functors $\pi f^g, \pi f'^{g'}:\pi Y^X\rightarrow\pi W^Z$ are homotopic as functors. There are a number of other examples throughout the book.

It is easy to see that $\varphi$ and $\varphi'$ are homotopic under Brown's definition iff there is a natural equivalence between them, i.e. a natural transformation from $\varphi$ to $\varphi'$, each component of which is an isomorphism. In this formulation it is clear that Brown's definition is stronger than Lee's. My question is this: in which contexts is each definition more useful? What are some arguments to favor one over the other?

setof base points for use in descent situations re Van Kampen's theorem, as strongly supported by Grothendieck in his Esquisse. Whether the simplicial approach is the "best" is another matter. Some motivitic homotopy work uses cubical sets with connections, for technical reasons that the simplicial did not work. See my 2018 paper in Indag. $\endgroup$