There are various approaches which work more or less well for different cases.
1) inner ysep
A simple solution could be set the inner y-separation legend style={inner ysep=5pt}:
\documentclass{standalone}
\usepackage{pgfplots}
\begin{document}
\begin{tikzpicture}
\begin{axis}[width=6cm, legend style={inner ysep=5pt}]
\addplot[domain=-2:2] {1};
\addlegendentry{$f(x)=\frac{1}{2\pi_{2_2}}$};
\addlegendentry{$f(x)=1$};
\end{axis}
\begin{scope}[shift={(5,0)}]
\begin{axis}[width=6cm, legend style={inner ysep=5pt}]
\addplot[domain=-2:2] {1};
\addlegendentry{$f(x)=1$};
\end{axis}
\end{scope}
\end{tikzpicture}
\end{document}
However you also increase the gap to the upper frame border:

2) text depth
legend style={nodes={text depth=1.5mm}}
Is a very elegant solution mentioned by @percusse in the comments. Some extra space is added below every item, also the last item, which maybe not desired in case the last item is no fraction.
3) row sep
If you have multiple legend entries (which you probably have, otherwise the legend is pointless) - and the last entry does not contain a fraction, then changing the row sep is the better option, as it doesn't adda gap neither on the top nor on bottom, just inbetween the items:
\documentclass{standalone}
\usepackage{pgfplots}
\begin{document}
\begin{tikzpicture}
\begin{axis}[width=6cm,legend style={row sep=5pt}]
\addplot[domain=-2:2] {1};
\addplot[domain=-2:2] {1};
\addlegendentry{$f(x)=\frac{1}{2\pi_{2_2}}$};
\addlegendentry{$f(x)=1$};
\end{axis}
\begin{scope}[shift={(5,0)}]
\begin{axis}[width=6cm]
\addplot[domain=-2:2] {1};
\addlegendentry{$f(x)=1$};
\end{axis}
\end{scope}
\end{tikzpicture}
\end{document}

4) parbox
Fiddling around with a \parbox could also be an option, case you just need a solution for a single particular item
\addlegendentry{\parbox[b][0.5cm][c]{2cm}{$f(x)=\frac{1\vphantom{2\pi^{2^2}}}{2\pi_{2_2}}$}};
5) semitransparent
Because of troubles like that I personally prefer something like:
\tikzset{semitransparent/.style = {draw=none, fill = white, fill opacity=0.8, text opacity = 1}}
and then
legend style={semitransparent}
over boxes.
legend style={nodes={text depth=1.5mm}}? – percusse Nov 08 '17 at 09:36\displaystyleto the expression to render it a bit better. But didn't test it. – percusse Nov 08 '17 at 09:41